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If you + don't derive profits, no royalty is due. Royalties are + payable to "Project Gutenberg Association/Carnegie-Mellon + University" within the 60 days following each + date you prepare (or were legally required to prepare) + your annual (or equivalent periodic) tax return. + +WHAT IF YOU *WANT* TO SEND MONEY EVEN IF YOU DON'T HAVE TO? +The Project gratefully accepts contributions in money, time, +scanning machines, OCR software, public domain etexts, royalty +free copyright licenses, and every other sort of contribution +you can think of. Money should be paid to "Project Gutenberg +Association / Carnegie-Mellon University". + +*END*THE SMALL PRINT! FOR PUBLIC DOMAIN ETEXTS*Ver.04.29.93*END* + + + + + +THE ORIGIN AND NATURE + +of the + +EMOTIONS + +Miscellaneous Papers + +BY + +GEORGE W. CRILE, M.D. + +PROFESSOR OF SURGERY, SCHOOL OF MEDICINE, WESTERN RESERVE UNIVERSITY +VISITING SURGEON TO THE LAKESIDE HOSPITAL, CLEVELAND + +EDITED BY +AMY F. ROWLAND, B. S. + + + + +PREFACE + + +IN response to numerous requests I have brought together into this volume +eight papers which may serve as a supplement to the volumes previously +published[*] and as a preface to monographs now in preparation. + + +[*] Surgical Shock, 1899; Surgery of the Respiratory System, 1899; +Problems Relating to Surgical Operations, 1901; Blood Pressure +in Surgery, 1903; Hemorrhage and Transfusion, 1909; +Anemia and Resuscitation, 1914; and Anoci-association, 1914 +(with Dr. W. E. Lower). + + +In the first of these addresses, the Ether Day Address, delivered at +the Massachusetts General Hospital in October, 1910, I first +enunciated the Kinetic Theory of Shock, the key to which was found +in laboratory researches and in a study of Darwin's "Expression +of the Emotions in Man and in Animals," whereby the phylogenetic +origin of the emotions was made manifest and the pathologic +identity of surgical and emotional shock was established. +Since 1910 my associates and I have continued our researches through-- +(a) Histologic studies of all the organs and tissues of the body; +(b) Estimation of the H-ion concentration of the blood in the emotions +of anger and fear and after the application of many other forms of stimuli; +(c) Functional tests of the adrenals, and (d) Clinical observations. + +It would seem that if the striking changes produced by fear +and anger and by physical trauma in the master organ of the body-- +the brain--were due to WORK, then we should expect to find +corresponding histologic changes in other organs of the body as well. +We therefore examined every organ and tissue of the bodies of animals +which had been subjected to intense fear and anger and to infection and +to the action of foreign proteins, some animals being killed immediately; +some several hours after the immediate effects of the stimuli had passed; +some after seances of strong emotion had been repeated several +times during a week or longer. + +The examination of all the tissues and organs of these animals +showed changes in three organs only, and with few exceptions in all +three of these organs--the brain, the adrenals, and the liver. +The extent of these changes is well shown by the photomicrographs +which illustrate the paper on "The Kinetic System" which is included +in this volume. This paper describes many experiments which show +that the brain, the adrenal, and the liver play together constantly +and that no one of these organs--as far at least as is indicated +by the histologic studies--can act without the co-operation +of the other two. + +Another striking fact which has been experimentally established +is that the deterioration of these three organs caused by emotion, +by exertion, and by other causes is largely counteracted, +if not exclusively, during sleep. If animals exhausted by the continued +application of a stimulus are allowed complete rest for a certain +number of hours, _*without sleep_, the characteristic histologic +appearance of exhaustion in the brain, adrenals, and liver is not +altered notably, whereas in animals allowed to sleep for the same +number of hours the histologic changes in these organs are lessened-- +in some cases obliterated even. + +This significant phenomenon and its relation will be dealt with in +a later monograph. + +Many of the arguments and illustrations by which the primary +premises were established are repeated--a few in all--many in +more than one of these addresses. It will be observed, however, +that the APPLICATION of these premises varies, and that their +SIGNIFICANCE broadens progressively. + +In the Ether Day Address the phylogenetic key supplied by Darwin was +utilized to formulate the principle that the organism reacts as a unit +to the stimuli of physical injury, of emotion, of infection, etc. +To the study of these reactions (transformations of energy) +the epoch-making work of Sherrington, "The Integrative Action +of the Nervous System," gave an added key by which the dominating +role of the brain was determined. Later the original work +of Cannon on the adrenal glands gave facts, and an experimental +method by which Darwin's phylogenetic theory of the emotions +was further elaborated in other papers, especially in the one +entitled "Phylogenetic Association in Relation to the Emotions," +read before The American Philosophical Society in April, 1911. +GEORGE W. CRILE. CLEVELAND, OHIO, _February, 1915_. + + + +CONTENTS PAGE PHYLOGENETIC ASSOCIATION IN RELATION TO CERTAIN MEDICAL +PROBLEMS. . . . . . . . . . . . . . . . . . . . . . . . . . .1 + +PHYLOGENETIC ASSOCIATION IN RELATION TO THE EMOTIONS . . . . +55 PAIN, LAUGHTER, AND CRYING. . . . . . . . . . . . . . . . . 77 + +THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND +BRAIN FUNCTIONS-EXPERIMENTAL AND CLINICAL . . . .111 + +A MECHANISTIC VIEW OF PSYCHOLOGY . . . . . . . . . . . . . .127 + +A MECHANISTIC THEORY OF DISEASE. . . . . . . . . . . . . . .157 + +THE KINETIC SYSTEM . . . . . . . . . . . . . . . . . . . . .173 + +ALKALESCENCE, ACIDITY, ANESTHESIA--A THEORY OF ANESTHESIA. .227 + +INDEX. . . . . . . . . . . . . . . . . . . . . . . . . . . .237 +THE ORIGIN AND NATURE OF THE EMOTIONS + +PHYLOGENETIC ASSOCIATION IN RELATION TO CERTAIN MEDICAL PROBLEMS[*] + + +[*] Address delivered at the Massachusetts General Hospital on +the sixty-fourth anniversary of Ether Day, Oct. 15, 1910. + + +The discovery of the anesthetic properties of ether and its practical +application to surgery must always stand as one of the great +achievements of medicine. It is eminently fitting that the anniversary +of that notable day, when the possibilities of ether were first +made known to the world, should be celebrated within these walls, +and whatever the topic of your Ether Day orator, he must fittingly +pause first to pay tribute to that great event and to the master +surgeons of the Massachusetts General Hospital. On this occasion, +on behalf of the dumb animals as well as on behalf of suffering humanity, +I express a deep sense of gratitude for the blessings of anesthesia. + +Two years ago, an historic appreciation of the discovery of ether +was presented here by Professor Welch, and last year an address +on medical research was given by President Eliot. I, therefore, +will not attempt a general address, but will invite your +attention to an experimental and clinical study. In presenting +the summaries of the large amount of data in these researches, +I acknowledge with gratitude the great assistance rendered by +my associates, Dr. D. H. Dolley, Dr. H. G. Sloan, Dr. J. B. Austin, +and Dr. M. L. Menten.[*] + + +[*] From the H. K. Cushing Laboratory of Experimental Medicine, +Western Reserve University, Cleveland. + + +The scope of this paper may be explained by a concrete example. +When a barefoot boy steps on a sharp stone there is an immediate discharge +of nervous energy in his effort to escape from the wounding stone. +This is not a voluntary act. It is not due to his own personal experience-- +his ontogeny--but is due to the experience of his progenitors +during the vast periods of time required for the evolution +of the species to which he belongs, _i. e_., his phylogeny. +The wounding stone made an impression upon the nerve receptors +in the foot similar to the innumerable injuries which gave origin +to this nerve mechanism itself during the boy's vast phylogenetic or +ancestral experience. The stone supplied the phylogenetic association, +and the appropriate discharge of nervous energy automatically followed. +If the sole of the foot be repeatedly bruised or crushed by a stone, +shock may be produced; if the stone be only lightly applied, +then the consequent sensation of tickling causes a discharge of +nervous energy. In like manner there have been implanted in the body +other mechanisms of ancestral or phylogenetic origin whose purpose +is the discharge of nervous energy for the good of the individual. +In this paper I shall discuss the origin and mode of action of some +of these mechanisms and their relation to certain phases of anesthesia. + +The word anesthesia--meaning WITHOUT FEELING--describes accurately +the effect of ether in anesthetic dosage. Although no pain +is felt in operations under inhalation anesthesia, the _*nerve +impulses excited by a surgical operation still reach the brain_. +We know that not every portion of the brain is fully anesthetized, +since surgical anesthesia does not kill. The question then is: +What effect has trauma under surgical anesthesia upon the part +of the brain THAT REMAINS AWAKE? If, in surgical anesthesia, +the traumatic impulses cause an excitation of the wide-awake cells, +are the remainder of the cells of the brain, despite anesthesia, +affected in any way? If so, they are prevented by the anesthesia from +expressing that influence in conscious perception or in muscular action. +Whether the ANESTHETIZED cells are influenced or not must be determined +by noting the physiologic functions of the body after anesthesia has +worn off, and in animals by an examination of the brain-cells as well. +It has long been known that the vasomotor, the cardiac, and the respiratory +centers discharge energy in response to traumatic stimuli applied +to various sensitive regions of the body during surgical anesthesia. +If the trauma be sufficient, exhaustion of the entire brain +will be observed after the effect of the anesthesia has worn off; +that is to say, despite the complete paralysis of voluntary +motion and the loss of consciousness due to ether, the traumatic +impulses that are known to reach the AWAKE centers in the medulla +also reach and influence every other part of the brain. +Whether or not the consequent functional depression and the morphologic +alterations seen in the brain-cells may be due to the low blood-pressure +which follows excessive trauma is shown by the following experiments: +The circulation of animals was first rendered STATIC by over-transfusion, +and was controlled by a continuous blood-pressure record on a drum, +the factor of anemia being thereby wholly excluded during the application +of the trauma and during the removal of a specimen of brain tissue +for histologic study. In each instance, morphologic changes +in the cells of all parts of the brain were found, but it required +much more trauma to produce brain-cell changes in animals whose +blood-pressure was kept at the normal level than in the animals +whose blood-pressure was allowed to take a downward course. +In the cortex and in the cerebellum, the changes in the brain-cells +were in every instance more marked than in the medulla. + +There is also strong NEGATIVE evidence that traumatic impulses +are not excluded by ether anesthesia from the part of the brain +that is apparently asleep. This evidence is as follows: +If the factor of fear be excluded, and if in addition the traumatic +impulses be prevented from reaching the brain by cocain[*] blocking, +then, despite the intensity or the duration of the trauma within +the zone so blocked, there follows no exhaustion after the effect +of the anesthetic disappears, and no morphologic changes are noted +in the brain-cells. + + +[*] Since the presentation of this paper, novocain has been +substituted for cocain in operations under anoci-association. + + +Still further negative evidence that inhalation anesthesia offers +little or no protection to the brain-cells against trauma is derived +from the following experiment: A dog whose spinal cord had been +divided at the level of the first dorsal segment, and which had +then been kept in good condition for two months, showed a recovery +of the spinal reflexes, such as the scratch reflex, etc. Such an +animal is known as a "spinal dog." Now, in this animal, the abdomen +and hind extremities had no direct nerve connection with the brain. +In this dog, continuous severe trauma of the abdominal viscera and of +the hind extremities lasting for four <p 5-7> hours was accompanied +by but slight change in either the circulation or in the respiration, +and by no microscopic alteration of the brain-cells (Fig. 1). Judging +from a large number of experiments on NORMAL dogs under ether, +such an amount of trauma would have caused not only complete +physiologic exhaustion of the brain, but also morphologic alterations +of all of the brain-cells and the physical destruction of many +(Fig. 2). We must, therefore, conclude that, although ether anesthesia +produces unconsciousness, it APPARENTLY PROTECTS NONE OF THE BRAIN-CELLS +against exhaustion from the trauma of surgical operations; ether is, +so to speak, but a veneer. Under nitrous oxid anesthesia there is +approximately only one-fourth as much exhaustion as is produced by equal +trauma under ether (Fig. 3). We must conclude, therefore, either that +nitrous oxid protects the brain-cells against trauma or that ether +predisposes the brain-cells to exhaustion as a result of trauma. +With these premises let us now inquire into the cause of this +exhaustion of the brain-cells. + + +The Cause of the Exhaustion of the Brain-cells as a Result of Trauma +of Various Parts of the Body under Inhalation Anesthesia + + +Numerous experiments on animals to determine the effect of ether +anesthesia _per se_, _i. e_., ether anesthesia without trauma, +showed that, although certain changes were produced, these included +neither the physiologic exhaustion nor the alterations in the +brain-cells which are characteristic of the effects of trauma. +On turning to the study of trauma, we at once found in the behavior +of individuals as a whole under deep and under light anesthesia +the clue to the cause of the discharge of energy, of the consequent +physiologic exhaustion, and of the morphologic changes in the brain-cells. + +If, in the course of abdominal operations, rough manipulations +of the parietal peritoneum be made, there will be frequently +observed a marked increase in the respiratory rate and an increase +in the expiratory force which may be marked by the production +of an audible expiratory groan. Under light ether anesthesia, +severe manipulations of the peritoneum often cause such vigorous +contractions of the abdominal muscles that the operator is greatly +hindered in his work. + +Among the unconscious responses to trauma under ether anesthesia +are purposeless moving, the withdrawal of the injured part, and, +if the anesthesia be sufficiently light and the trauma sufficiently +strong, there may be an effort toward escape from the injury. +In injury under ether anesthesia every grade of response may be seen, +from the slightest change in the respiration or in the blood-pressure +to a vigorous defensive struggle. As to the purpose of these +subconscious movements in response to injury, there can be no doubt-- +THEY ARE EFFORTS TO ESCAPE FROM THE INJURY. + +Picture what would be the result of a formidable abdominal operation +extending over a period of half an hour or more on an unanesthetized +human patient, during which extensive adhesions had been broken up, +or a large tumor dislodged from its bed! In such a case, +would not the nervous system discharge its energy to the utmost +in efforts to escape from the injury, and would not the patient suffer +complete exhaustion? If the traumata under inhalation anesthesia +are sufficiently strong and are repeated in sufficient numbers, +the brain-cells are finally deprived of their dischargeable nervous +energy and become exhausted just as exhaustion follows such strenuous +and prolonged muscular exertion as is seen in endurance tests. +Whether the energy of the brain be discharged by injury under anesthesia +or by ordinary muscular exertion, identical morphologic changes are +seen in the nerve-cells. In shock from injury (Fig. 2), in exhaustion +from overwork (Hodge and Dolley) (Fig. 4), and in exhaustion from pure fear +(Fig. 5), the resultant general functional weakness is similar-- +in each case a certain length of time is required to effect recovery, +and in each there are morphologic changes in the brain-cells. It +is quite clear that in each of these cases the altered function +and form of the brain-cells are due to an _*excessive discharge +of nervous energy_. This brings us to the next question: +What determines the discharge of energy as a result of trauma +with or without inhalation anesthesia? + + +The Cause of the Discharge of Nervous Energy as a Result of Trauma +under Inhalation Anesthesia and under Normal Conditions + + +I looked into this problem from many viewpoints and there seemed +to be no solution until it occurred to me to seek the explanation +in certain of the postulates which make up the doctrine of evolution. +I realize fully the difficulty and the danger in attempting +to reach the generalization which I shall make later and in +the hypothesis I shall propose, for there is, of course, no direct +final proof of the truth of even the doctrine of evolution. +It is idle to consider any experimental research into the cause +of phenomena that have developed by natural selection during +millions of years. Nature herself has made the experiments on +a world-wide scale and the data are before us for interpretation. +Darwin could do no more than to collect all available facts and then +to frame the hypothesis by which the facts were best harmonized. +Sherrington, that masterly physiologist, in his volume entitled +"The Integrative Action of the Nervous System," shows clearly how +the central nervous system was built up in the process of evolution. +Sherrington has made free use of Darwin's doctrine in explaining +physiologic functions, just as anatomists have extensively +utilized it in the explanation of the genesis of anatomic forms. +I shall assume, therefore, that the discharge of nervous energy is +accomplished by the application of the laws of inheritance and association, +and I conclude that this hypothesis will explain many clinical phenomena. +I shall now present such evidence in favor of this hypothesis as time +and my limitations will admit, after which I shall point out certain +clinical facts that may be explained by this hypothesis. + +According to the doctrine of evolution, every function owes +its origin to natural selection in the struggle for existence. +In the lower and simpler forms of animal life, indeed, in our +human progenitors as well, existence depended principally upon +the success with which three great purposes were achieved: +(1) Self-defense against or escape from enemies; (2) the acquisition +of food; and (3) procreation; and these were virtually the only purposes +for which nervous energy was discharged. In its last analysis, +in a biologic sense, this statement holds true of man today. +Disregarding for the present the expenditure of energy for procuring +food and for procreation, let us consider the discharge of energy +for self-preservation. The mechanisms for self-defense which we +now possess were developed in the course of vast periods of time +through innumerable intermediary stages from those possessed by +the lowest forms of life. One would suppose, therefore, that we must +now be in possession of mechanisms which still discharge energy on +adequate stimulation, but which are not suited to our present needs. +We shall point out some examples of such unnecessary mechanisms. +As Sherrington has stated, our skin, in which are implanted many +receptors for receiving specific stimuli which are transmitted +to the brain, is interposed between ourselves and the environment +in which we are immersed. When these stimuli reach the brain, +there is a specific response, principally in the form of +muscular action. Now, each receptor can be adequately stimulated +only by the particular factor or factors in the environment +which created the necessity for the existence of that receptor. +Thus there have arisen receptors for touch, for temperature, +for pain, etc. The receptors for pain have been designated _nociceptors_ +(nocuous or harmful) by Sherrington. + +On the basis of natural selection, nociceptors could have developed +in only those regions of the body which have been exposed to injury +during long periods of time. On this ground the finger, because it +is exposed, should have many nociceptors, while the brain, though the +most important organ of the body, should have no nociceptors because, +during a vast period of time, it has been protected by a skull. +Realizing that this point is a crucial one, Dr. Sloan and I made a series +of careful experiments. The cerebral hemispheres of dogs were exposed +by removing the skull and dura under ether and local anesthesia. +Then various portions of the hemispheres were slowly but +completely destroyed by rubbing them with pieces of gauze. +In some instances a hemisphere was destroyed by burning. +In no case was there more than a slight response of the centers governing +circulation and respiration, and no morphologic change was noted +in an histologic study of the brain-cells of the uninjured hemisphere. +The experiment was as completely negative as were the experiments +on the "spinal dog." Clinically I have confirmed these experimental +findings when I have explored the brains of conscious patients +with a probe to determine the presence of brain tumors. +Such explorations elicited neither pain nor any evidence of altered +physiologic functions. The brain, therefore, contains no mechanism-- +no nociceptors--the direct stimulation of which can cause +a discharge of nervous energy in a self-defensive action. +That is to say, direct injury of the brain can cause no purposeful +nerve-muscular action, while direct injury of the finger does cause +purposeful nerve-muscular action. In like manner, the deeper portions +of the spinal region have been sheltered from trauma and they, too, +show but little power of causing a discharge of nervous energy +on receiving trauma. The various tissues and organs of the body +are differently endowed with injury receptors--the nociceptors +of Sherrington. The abdomen and chest when traumatized stand first +in their facility for causing the discharge of nervous energy, _i. +e_., THEY STAND FIRST IN SHOCK PRODUCTION. Then follow the extremities, +the neck, and the back. It is an interesting fact also that different +types of trauma elicit different responses as far as the consequent +discharge of energy is concerned. + +Because it is such a commonplace observation, one scarcely realizes +the importance of the fact that clean-cut wounds inflicted +by a razor-like knife cause the least reaction, while a tearing, +crushing trauma causes the greatest response. It is a suggestive fact +that the greatest shock is produced by any technic which imitates +the methods of attack and of slaughter used by the carnivora. +_*In the course of evolution, injuries thus produced may well have +been the predominating type of traumata to which our progenitors +were subjected_. In one particular respect there is an analogy between +the response to trauma of some parts of the body of the individuals +of a species susceptible to shock and the response to trauma of the +individuals in certain other great divisions of the animal kingdom. +Natural selection has protected the crustaceans against their +enemies by protective armor, _e. g_., the turtle and the armadillo; +to the birds, it has given sharp eyes and wings, as, for instance, +the wild goose to another species--the skunk--it has given a noisome odor +for its protection. The turtle, protected by its armor against trauma, +is in a very similar position to that of the sheltered brain +of man and, like the brain, the turtle does not respond to trauma +by an especially active self-protective nerve-muscular response, +but merely withdraws its head and legs within the armored protection. +It is proverbially difficult to exhaust or to kill this animal by trauma. +The brain and other phylogenetically sheltered parts likewise give no +exhausting self-protective nerve-muscular response to trauma. The skunk +is quite effectively protected from violence by its peculiar odor. +This is indicated not only by the protective value of the odor itself, +but also by the fact that the skunk has no efficient nerve-muscular +mechanism for escape or defense; it can neither run fast nor can it +climb a tree. Moreover, in encounters it shows no fear and backs +rather than runs. The armadillo rolls itself into a ball for defense. +On these premises we should conclude that the turtle, +the armadillo, and the skunk have fewer nociceptors than has +a dog or man, and that they would show less response to trauma. +In two carefully conducted experiments on skunks and two on armadillos +(an insufficient number) the energy discharged in response to severe +and protracted trauma of the abdominal viscera was very much less than +in similar experiments on dogs, opossums, pigs, sheep, and rabbits. +It was indeed relatively difficult to exhaust the skunks and armadillos +by trauma. These experiments are too few to be conclusive, +but they are of some value and furnish an excellent lead. +It seems more than a coincidence that proneness to fear, +distribution of nociceptors, and susceptibility to shock go +hand-in-hand in these comparative observations (Figs. 6, 7, and 8). + +The discharge of energy caused by an adequate mechanical stimulation +of the nociceptors is best explained in accordance with the law +of phylogenetic association. That is, injuries awaken those reflex +actions which by natural selection have been developed for the purpose +of self-protection. Adequate stimulation of the nociceptors for pain +is not the only means by which a discharge of nervous energy is caused. +Nervous energy may be discharged also by adequate stimulation +of the various ticklish regions of the body; the entire skin +surface of the body contains delicate ticklish receptors. +These receptors are closely related to the nociceptors for pain, +and their adequate stimulation by an insect-like touch +causes a discharge of energy,--a nerve-muscular reaction,-- +resembling that developed for the purpose of brushing off insects. +This reflex is similar to the scratch reflex in the dog. +The discharge of energy is almost wholly independent of the will +and is a self-protective action in the same sense as is the response +to pain stimuli. The ear in man and in animals is acutely ticklish, +the adequate stimulus being any foreign body, especially a buzzing, +insect-like contact. The discharge of nervous energy in horses +and in cattle on adequate stimulation of the ticklish receptors +of the ear is so extraordinary that in the course of evolution it +must have been of great importance to the safety of the animal. +A similar ticklish zone guards the nasal chambers, the discharge of energy +here taking a form which effectively dislodges the foreign body. +The larynx is exquisitely ticklish, and, in response to any adequate +stimulus, energy is discharged in the production of a vigorous cough. +The mouth and pharynx have active receptors which cause the rejection +of noxious substances. The conjunctival reflex, though not +classed as ticklish, is a most efficient self-protective reflex. +I assume that there is no doubt as to the relation between +the adequate stimuli and the nerve-muscular response of the various +ticklish receptors of the surface of the skin, of the ear, +the nose, the eye, and the larynx. These mechanisms were developed +by natural selection as protective measures against the intrusion +of insects and foreign bodies into regions of great importance. +The discharge of energy in these instances is in accordance +with the laws of inheritance and association. The other ticklish +points which are capable of discharging vast amounts of energy +are the lateral chest-wall, the abdomen, the loins, the neck, +and the soles of the feet. The type of adequate stimuli of the soles +of the feet, the distribution of the ticklish points upon them, +and the associated response, leave no doubt that these ticklish points +were long ago established as a means of protection from injury. +Under present conditions they are of little value to man. + +The adequate stimulus for the ticklish points of the ribs, +the loins, the abdomen, and the neck is deep isolated pressure, +probably the most adequate being pressure by a tooth-shaped body. +The response to tickling in these regions is actively and obviously +self-defensive. The horse discharges energy in the form of a kick; +the dog wriggles and makes a counter-bite; the man makes efforts +at defense and escape. + +There is strong evidence that the deep ticklish points of the body +were developed through vast periods of fighting with teeth and claws +(Fig. 9). Even puppies at play bite each other in their ticklish +points and thus give a recapitulation of their ancestral battles +and of the real battles to come (Fig. 10). The mere fact that animals +fight effectively in the dark and always according to the habit +of their species supports the belief that the fighting of animals +is not an intellectual but a reflex process. There are no rules +which govern the conduct of a fight between animals. The events +follow each other with such kaleidoscopic rapidity that the process +is but a series of automatic stimulations and physiologic reactions. +Whatever their significance, therefore, it is certain that man did +not come either accidentally or without purpose into possession +of the deep ticklish regions of his chest and abdomen. +Should any one doubt the vast power that adequate stimulation +of these regions possesses in causing the discharge of energy, +let him be bound hand and foot and vigorously tickled for an hour. +What would happen? He would be as completely exhausted as though he had +experienced a major surgical operation or had run a Marathon race. + +A close analogy to the reflex process in the fighting of animals +is shown in the role played by the sexual receptors in conjugation. +Adequate stimulation of either of these two distinct groups +of receptors, the sexual and the noci, causes specific behavior-- +the one toward embrace, the other toward repulsion. Again, one of +the most peremptory causes of the discharge of energy is that due +to an attempt to obstruct forcibly the mouth and the nose so that +asphyxia is threatened. Under such conditions neither friend +nor foe is trusted, and a desperate struggle for air ensues. +It will be readily granted that the reactions to prevent suffocation +were established for the purpose of self-preservation, but the discharge +of nerve-muscular energy to this particular end is no more specific +and no more shows adaptive qualities than do the preceding examples. +Even the proposal to bind one down hand and foot excites resentment, +a feeling originally suggested by the need for self-preservation. +No patient views with equanimity the application of shackles +as a preparation for anesthesia. + +We have now considered some of the causes of those discharges of nervous +energy which result from various types of harmful physical contact, +and have referred to the analogous, though antithetical, +response to the stimulation of the sexual receptors. +The response to the adequate stimuli of each of the several receptors +is a discharge of nerve-muscular energy of a specific type; that is, +there is one type of response for the ear, one for the larynx, +one for the pharynx, another for the nose, another for the eye, +another for the deep ticklish points of the chest and the abdomen, +quite another for the delicate tickling of the skin, and still +another type of response to sexual stimuli. + +According to Sherrington, a given receptor has a low threshold +for only one, its own specific stimulus, and a high threshold +for all others; that is, the doors that guard the nerve-paths +to the brain are opened only when the proper password is received. +According to Sherrington's law, the individual as a whole responds +to but one stimulus at a time, that is, only one stimulus +occupies the nerve-paths which carry the impulses as a result +of which acts are performed, _i. e_., the final common path. +As soon as a stronger stimulus reaches the brain it dispossesses +whatever other stimulus is then occupying the final common path-- +the path of action. The various receptors have a definite order +of precedence over each other (Sherrington). For example, the impulse +from the delicate ticklish points of the skin, whose adequate +stimulus is an insect-like contact, could not successfully compete +for the final common path with the stimulus of a nociceptor. +The stimulus of a fly on the nose would be at once superseded by +the crushing of a finger. In quick succession do the various receptors +(Sherrington) occupy the final common path, but each stimulus is for +the time the sole possessor, hence the nervous system is integrated +(connected) to act as a whole. Each individual at every moment +of life has a limited amount of dischargeable nervous energy. +This energy is at the disposal of any stimulus that obtains possession +of the final common path, and results in the performance of an act. +Each discharge of energy is subtracted from the sum total of stored +energy and, whether the subtractions are made by the excitation +of nociceptors by trauma, by tickling, by fighting, by fear, +by flight, or by the excitation of sexual receptors, by any +of these singly or in combination with others, the sum total of +the expenditure of energy, if large enough, produces exhaustion. +Apparently there is no distinction between that state of exhaustion +which is due to the discharge of nervous energy in response +to trauma and that due to other causes. The manner of the +discharge of energy is specific for each type of stimulation. +On this conception, traumatic shock takes its place as a natural +phenomenon and is divested of its mask of mystery. + + +The Discharge of Energy through Stimulation of the Distance Receptors, +or through Representation of Injury (Psychic) + + +We will now turn from the discussion of the discharge of nervous energy by +mechanical stimuli to the discharge of energy through mental perception. +_Phylogenetic_ association may result from stimulation of the distance +receptors through sight, hearing, smell, or by a representation +of physical experiences, as well as from physical contact. +The effect upon the organism of the representation of injury +or of the perception of danger through the distance receptors is +designated FEAR. Fear is as widely distributed in nature as is its cause, +that is, fear is as widely distributed as injury. Animals under +the stimulus of fear, according to W. T. Hornaday, not only may exhibit +preternatural strength, but also may show strategy of the highest order, +a strategy not seen under the influence of a lesser stimulus. +In some animals fear is so intense that it defeats escape; this is +especially true in the case of birds in the presence of snakes. +The power of flight has endowed the bird with an easy means of escape +from snakes, especially when the encounter is in the tops of trees. +Here the snake must move cautiously, else he will lose his equilibrium; +his method of attack is by stealth. When the snake has stalked +its prey, the bird is often so overcome by fear that it cannot fly +and so becomes an easy victim (Fig. 11). The phenomena of fear +are described by Darwin as follows: + +"Fear is often preceded by astonishment, and is so near akin to it that +both lead to the senses of sight and hearing being instantly aroused. +In both cases the eyes and mouth are widely opened and the +eyebrows raised. The frightened man at first stands like a statue, +motionless and breathless, or crouches down as if instinctively +to escape observation. The heart beats quickly and violently, +so that it palpitates or knocks against the ribs. * * * That the skin +is much affected under the sense of great fear we see in the marvelous +and inexplicable manner in which perspiration immediately exudes from it. +This exudation is all the more remarkable as the surface is then cold, +and hence the term, `a cold sweat'; whereas the sudorific glands +are properly excited into action when the surface is heated. +The hairs also on the skin stand erect, and the superficial +muscles shiver. In connection with the disturbed action of the heart, +the breathing is hurried. The salivary glands act imperfectly; +the mouth becomes dry, and is often opened and shut. I have also +noticed that under slight fear there is a strong tendency to yawn. +One of the best-marked symptoms is the trembling of all the +muscles of the body; and this is often first seen in the lips. +From this cause, and from the dryness of the mouth, the voice +becomes husky and indistinct, or may altogether fail. +* * * As fear increases into agony of terror, we behold, as under +all violent emotions, diversified results. The heart beats wildly, +or may fail to act and faintness ensues; there is death-like pallor; +the breathing is labored; the wings of the nostrils are widely dilated; +`there is a gasping and convulsive motion of the lips, a tremor +on the hollow cheek, a gulping and catching of the throat'; +the uncovered and protruding eyeballs are fixed on the object of terror; +or they may roll restlessly from side to side. * * * The pupils +are said to be enormously dilated. All the muscles of the body +may become rigid, or may be thrown into convulsive movements. +The hands are alternately clenched and opened, often with a +twitching movement. The arms may be protruded, as if to avert +some dreadful danger, or may be thrown wildly over the head. +* * * In other cases there is a sudden and uncontrollable tendency +to headlong flight; and so strong is this that the boldest soldiers +may be seized with a sudden panic. As fear rises to an extreme pitch, +the dreadful scream of terror is heard. Great beads of sweat +stand on the skin. All the muscles of the body are relaxed. +Utter prostration soon follows, and the mental powers fail. +The intestines are affected. The sphincter muscles cease +to act and no longer retain the contents of the body. +* * * Men, during numberless generations, have endeavored +to escape from their enemies or danger by headlong flight, +or by violently struggling with them; and such great exertions +will have caused the heart to beat rapidly, the breathing to +be hurried, the chest to heave, and the nostrils to be dilated. +As these exertions have often been prolonged to the last extremity, +the final result will have been utter prostration, pallor, perspiration, +trembling of all the muscles, or their complete relaxation. +And now, whenever the emotion of fear is strongly felt, though it +may not lead to any exertion, the same results tend to reappear, +through the force of inheritance and association"[*] (Fig. 12). + + +[*] Darwin: Expression of the Emotions in Man and Animals. + + +In an experimental research, we found evidence that the physiologic +phenomena of fear have a physical basis. This evidence is found +in the morphologic alterations in the brain-cells, which are similar +to those observed in certain stages of surgical shock and in fatigue +from muscular exertion (Figs. 2, 4, 5, and 13). For the present, +we shall assume that fear is a REPRESENTATION of trauma. +Because fear was created by trauma, fear causes a discharge of the energy +of the nervous system by the law of phylogenetic association. +The almost universal fear of snakes, of blood, and of death +and dead bodies may have such a phylogenetic origin. +It was previously stated that under the stimulus of fear animals +show preternatural strength. An analysis of the phenomena of fear +shows that, as far as can be determined, all the functions of the body +requiring the expenditure of energy, and which are of no direct +assistance in the effort toward self-preservation, are suspended. +In the voluntary expenditure of muscular energy, as in the chase, +the suspension of other functions is by no means so complete. +Fear and trauma may drain to the last dreg the dischargeable +nervous energy, and, therefore, the greatest possible exhaustion +may be produced by fear and trauma. + + +Summation + +In the discharge of energy, summation plays an important role. +Summation is attained by the repetition of stimuli at such a rate +that each succeeding stimulus is applied before the nerve-cells +have returned to the resting stage from the preceding stimulus. +If drops of water fall upon the skin from a sufficient height to cause +the slightest unpleasant sensation, and at such a rate that before +the effect of the stimulus of one drop has passed another drop +falls in precisely the same spot, there will be felt a gradually +increasing painful sensation which finally becomes unbearable. +This is summation of stimuli. When, for a long time, a patient +requires frequent painful wound dressings, there is a gradual +increase in the acuteness of the pain of the receptors. +This is caused by summation. In a larger sense, the entire behavior +of the individual gives considerable evidence of summation, _e. +g_., in the training of athletes, the rhythmic discharge of muscular +energy at such intervals that the resting stage is not reached +before a new exercise is given results in a gradual ascent +in efficiency until the maximum is reached. This is summation, +and summation plays a large role in the development of both normal +and pathologic phenomena. + +We have now pointed out the manner in which at least +a part of the nervous energy of man may be discharged. +The integrative action of the nervous system and the discharge +of nervous energy by phylogenetic association may be illustrated +by their analogy to the action of an electric automobile. +The electric automobile is composed of four principal parts: +The motor and the wheels (the muscular system and the skeleton); +the cells of the battery containing stored electricity +(brain-cells, nervous energy); the controller, which is connected +with the cells by wiring (the receptors and the nerve-fibers); +and an accelerator for increasing the electric discharge +(thyroid gland?). The machine is so constructed that it acts +as a whole for the accomplishment of a single purpose. +When the controller is adjusted for going ahead (adequate stimulus +of a receptor), then the conducting paths (the final common path) +for the accomplishment of that purpose are all open to the flow of +the current from the battery, and the vehicle is integrated to go ahead. +It spends its energy to that end and is closed to all other impulses. +When the controller is set for reverse, by this adequate stimulus +the machine is integrated to back, and the battery is closed to all +other impulses. Whether integrated for going forward or backward, +if the battery be discharged at a proper rate until exhausted, +the cells, though possessing no more power (fatigue), have sustained +no further impairment of their elements than that of normal wear +and tear. Furthermore, they may be restored to normal activity +by recharging (rest). If the vehicle be placed against a stone wall, +and the controller be placed at high-speed (trauma and fear), +and if the accelerator be used as well (thyroid secretion?), though +the machine will not move, not only will the battery soon be exhausted, +but the battery elements themselves will be seriously damaged +(exhaustion--surgical shock). + +We have now presented some evidence that nervous energy is +discharged by the adequate stimulation of one or more of the various +receptors that have been developed in the course of evolution. +In response to an adequate stimulus, the nervous system is +integrated for a specific purpose by the stimulated receptor, +and but one stimulus at a time has possession of the final common path-- +the nerve mechanisms for action. The most numerous receptors +are those for harmful contact; these are the nociceptors. +The effect of the adequate stimulus of a nociceptor is like that of +pressing an electric button that sets great machinery in motion. + +With this conception, the human body may be likened to a +musical instrument--an organ--the keyboard of which is composed +of the various receptors, upon which environment plays the many +tunes of life; and written within ourselves in symbolic language +is the history of our evolution. The skin may be the "Rosetta Stone" +which furnishes the key. + + +Anoci-association + + +By the law of phylogenetic association, we are now prepared +to make a practical application of the principles of the discharge +of nervous energy. In the case of a surgical operation, if fear +be excluded and if the nerve-paths between the field of operation +and the brain be blocked with cocain,[*] no discharge of energy will be +caused by the operation; hence no shock, no exhaustion, can result. +Under such conditions the nervous system is protected against +noci-association, resulting from noci-perception or from an adequate +stimulation of nociceptors. The state of the patient in whom all +noci-associations are excluded can be described only by coining +a new word. That word is "anoci-association" (Fig. 14). + + +[*] See footnote, page 4.@@@ + + +The difference between anesthesia and anoci-association is that, +although _inhalation anesthesia_ confers the beneficent loss of +consciousness and freedom from pain, it does not prevent the nerve +impulses from reaching and influencing the brain, and therefore does +not prevent surgical shock nor the train of later nervous impairments +so well described by Mumford. _Anoci-association_ excludes fear, +pain, shock, and postoperative neuroses. _Anoci-association_ is +accomplished by combining the special management of patients +(applied psychology), morphin, inhalation anesthesia, +and local anesthesia. + +We have now presented in summary much of the mass of experimental +and clinical evidence we have accumulated in support of our +principal theme, which is that the discharge of nervous energy is +accomplished in accordance with the law of phylogenetic association. +If this point seems to have been emphasized unduly, it is because +we expect to rear upon this foundation a clinical structure. +How does this hypothesis apply to surgical operations? + + +Prevention of Shock by the Application of the Principle of +Anoci-association + + + +Upon this hypothesis a new principle in operative surgery is founded, _i. +e_., operation during the state of _anoci-association_. Assuming that +no unfavorable effect is produced by the anesthetic and that there is +no hemorrhage, the cells of the brain cannot be exhausted in the course +of a surgical operation except by fear or by trauma, or by both. +Fear may be excluded by narcotics and special management until +the patient is rendered unconscious by inhalation anesthesia. +Then if, in addition to inhalation anesthesia, the nerve-paths +between the brain and the field of operation are blocked with +cocain,[*] the patient will be placed in the beneficent state of +_anoci-association_, and at the completion of the operation will be +as free from shock as at the beginning. In so-called "fair risks" +such precautions may not be necessary, but in cases handicapped +by infections, by anemia, by previous shock, and by Graves' +disease, etc., anoci-association may become vitally important. + + +[*] See footnote, page 4.@@@ + + +Graves' Disease + + +By applying the principle of the discharge of nervous energy by +phylogenetic association, and by making the additional hypothesis +that in the discharge of nervous energy the thyroid gland is stimulated +through the nervous system, we can explain many of the phenomena +of Graves' disease and may possibly discover some of the factors +which explain both its genesis and its cure. + +In the wild state of animal life in which only the fittest +survive in the struggle for existence, every point of advantage +has its value. An animal engaged in battle or in a desperate +effort to escape will be able to give a better account of itself +if it have some means of accelerating the discharge of energy-- +some influence like that of pouring oil upon the kindling fire. +There is evidence, though perhaps it is not conclusive, +that such an influence is exerted by the thyroid gland. +In myxedema, a condition characterized by a lack of thyroid secretion, +there is dulness of the reflexes and of the intellect, a lowered +muscular power, and generally a sluggish discharge of energy. +In Graves' disease there is an excessive production of thyroid secretion. +In this disease the reflexes are increased, the discharge of +energy is greatly facilitated, and metabolism is at a maximum. +The same phenomena occur also after the administration of thyroid +extract in large doses to normal subjects. In the course of +sexual activities there is an increased action of the thyroid, +which is indicated by an increase in its size and vascularity. +That in fear and in injury the thyroid, in cases of Graves' +disease, is probably stimulated to increased activity is indicated +by the increased activity of the thyroid circulation, by an increase +in the size of the gland, by the histologic appearance of activity +in the nuclei of the cells, and by an increase of the toxic symptoms. +Finally, Asher has stated that electric stimulation of the nerve supply +of the thyroid causes an increased secretion. The origin of many cases +of Graves' disease is closely associated with some of the causes +of the discharge of nervous energy, depressive influences especially, +such as nervous shocks, worry and nervous strain, disappointment in love, +business reverses, illness and death of relatives and friends. +The association of thyroid activity with procreation is well known, +hence the coincidence of a strain of overwork or of fear with +the sexual development of maturing girls is obviously favorable +to the incidence of Graves' disease. The presence of a colloid goiter +is a suitable soil for the development of Graves' disease, and I +fully recognize also the evidence that infection or auto-intoxication +may be contributing factors and must be assigned their role. + +I have never known a case of Graves' disease to be caused by success +or happiness alone, or by hard physical labor unattended by +psychic strain, or to be the result of energy voluntarily discharged. +Some cases seem to have had their origin in overdosage with thyroid +extract in too vigorous an attempt to cure a colloid goiter. +One of the most striking characteristics of Graves' disease is +the patient's loss of control and his increased susceptibility +to stimuli, especially to trauma and to fear and to the administration +of thyroid extract. It has been shown that the various causes +of the discharge of nervous energy produce alterations in the nervous +system and probably in the thyroid gland. This is especially +true of the fear stimulus, and has been clearly demonstrated +in the brains of rabbits which had been subjected to fear alone +(Fig. 13). Of special interest was the effect of daily fright. +In this case the brain-cells showed a distinct change, although the animal +had been subjected to no fear for twenty-four hours before it was killed +(Fig. 13 C. Now, a great distinction between man and the lower +animals is the greater control man has acquired over his actions. +This quality of control, having been phylogenetically most recently +acquired, is the most vulnerable to various NOCUOUS influences. +The result of a constant noci-integration may be a wearing-out +of the control cells of the brain. In a typical case of Graves' +disease a marked morphologic change in the brain-cells has +been demonstrated (Fig. 15). As has been previously stated, +the origin of many cases of Graves' disease is associated +with some noci-influence. If this influence causes stimulation +of both the brain and the thyroid, its excessive action may cause +impairment of the brain and also hyperplasia of the thyroid. +As self-control is impaired, fear obtains an ascendency and, +_pari passu_, stimulates the thyroid still more actively (Fig. 16). +Finally, the fear of the disease itself becomes a noci-stimulus. +As the thyroid secretion causes an increase in the facility +with which nervous energy is discharged, a pathologic reciprocal +interaction is established between the brain and the thyroid. +The effect of the constantly recurring stimulus of the noci-influence +is heightened by summation. This reciprocal goading may +continue until either the brain or the thyroid is destroyed. +If the original noci-stimulus is withdrawn before the fear of the +disease becomes too strong, and before too much injury to the brain +and the thyroid has been inflicted, a spontaneous cure may result. +Recovery may be greatly facilitated by complete therapeutic rest. +A cure implies the return of the brain-cells to their normal state, +with the reestablishment of the normal self-control and the +restoration of the thyroid to its normal state, when the impulses +of daily life will once more have possession of the final +common path and the noci-influence will be dispossessed. +The discovery of the real cause of a given case of Graves' disease is +frequently difficult because it may be of a painful personal nature. +Of extreme interest is the fact that, in the acute stage, +the patient may be unable to refer to the exciting cause without +exhibiting an exacerbation of the symptoms of the disease. +I presume no case should be regarded as cured until reference +can be made to its cause without an abnormal reaction. +It has been established that in Graves' disease injury to any part +of the body, even under inhalation anesthesia, causes an exacerbation +of the disease. Fear alone may cause an acute exacerbation. +These acute exacerbations are frequently designated "hyperthyroidism" +and are the special hazard of operation. + +In applying the principle of anoci-association in operations on +patients with Graves' disease there is scarcely a change in the pulse, +in the respiration, or in the nervous state at the close of the operation. +I know no remedy which can obviate the effect of the inflowing +stimuli from the wound after the cocain[*] has worn off.[t] It +is necessary, therefore, + + +Beats 70 80 90 100 110 120 + + + +Ether ******* ******** ******** ******** ******** + + + +N2O ******* ******** ******** ******** * + + + +Anoci. ******* ******** ******** ** not to venture too far +in serious cases. Since the adoption of this new method +(anoci-association) my operative results have been so vastly improved +that I now rarely regard any case of Graves' disease as inoperable, +at least to the extent of contraindicating a double ligation (Fig. 17). + + +[*] See footnote, page 4.@@@ + +[t] In later papers and in "Anoci-association" (Crile and Lower) +methods of combating postoperative hyperthyroidism are fully discussed. + + +If we believe that, in accordance with the law of phylogenetic association, +a continuous stimulation of both the brain and the thyroid gland, +accelerated by summation, plays a role in the establishment +of the pathologic interaction seen in Graves' disease, then it +is but the next step to assume that if the nerve connection between +the brain and the thyroid be severed, or if the lobe be excised +and the patient reinforced by a sojourn in a sanatorium or in some +environment free from former noci-associations, he may be restored +to normal health, provided that the brain-cells, the heart, +or other essential organs have not suffered irreparable damage. +There are still many missing links in the solution of this problem, +and the foregoing hypotheses are not offered as final, although from +the viewpoint of the surgeon many of the phenomena of this +disease are explicable. + + +Sexual-Neurasthenia + + +The state of sexual neurasthenia is in many respects analogous +to that of Graves' disease. In the sexual reflexes, summation leads +to a hyperexcitability by psychic and mechanical stimuli of a +specific type which is analogous to the hyperexcitability in Graves' +disease under trauma and fear; the explanation of both conditions +is based on the laws of the discharge of energy by phylogenetic +association and summation. It would be interesting to observe +the effect of interrupting the nerve impulses from the field of +the sexual receptors by injections of alcohol, or by other agencies, +so as to exclude the associational stimuli until the nervous +mechanism has again become restored to its normal condition. +Interpretation of Some of the Phenomena of Certain Diseases of the +Abdomen in Accordance with the Hypothesis of Phylogenetic Association + + +The law of phylogenetic association seems to explain many +of the phenomena of certain lesions in the abdominal cavity. +The nociceptors in the abdomen, like nociceptors elsewhere, have been +established as a result of some kind of injury to which during +vast periods of time this region has been frequently exposed. +On this premise, we should at once conclude that there are no +nociceptors for heat within the abdomen because, during countless years, +the intra-abdominal region never came into contact with heat. +That this inference is correct is shown by the fact that the +application of a thermocautery to the intestines when completing +a colostomy in a conscious patient is absolutely painless. +One would conclude also that there are no touch receptors in the +abdominal viscera, and therefore no sense of touch in the peritoneum. +Just as the larynx, the ear, the nose, the sole of the foot, +and the skin have all developed the specific type of nociceptors +which are adapted for their specific protective purposes, and which, +when adequately stimulated, respond in a specific manner in accordance +with the law of phylogenetic association, so, the abdominal viscera +have developed equally specific nociceptors as a protection against +specific nocuous influences. The principal harmful influences +to which the abdominal viscera have been exposed during vast periods +of time are deep tearing injuries by teeth and claws in the innumerable +struggles of our progenitors with each other and with their enemies +(Fig. 9); peritonitis caused by perforations of the intestinal +tract from ulcers, injuries, appendicitis, gall-stones, etc.; +and overdistention of the hollow viscera by various forms of obstruction. +Whatever may be the explanation, it is a fact that the type +of trauma which results from fighting corresponds closely with +that which causes the most shock in the experimental laboratory. +Division of the intestines with a sharp knife causes no pain, +but pulling on the mesentery elicits pain. Ligating the stump +of the appendix causes sharp, cramp-like pains. Sharp division +of the gall-bladder causes no pain, but distention, which is +the gall-bladder's most common pathologic state, produces pain. +Distention of the intestine causes great pain, but sharp cutting or burning +causes none. In the abdominal viscera, as in the superficial parts, +nociceptors have presumably been developed by specific harmful +influences and each nociceptor is open to stimulation only by a +stimulus of the particular type that produced it. + +As a result of the excitation of nociceptors, with which pain +is associated, the routine functions, such as peristalsis, secretion, +and absorption are dispossessed from the control of their respective +nervous mechanisms, just as they are inhibited by fear. This hypothesis +explains the loss of weight, the lassitude, the indigestion, +the constipation, and the many alterations in the functions of the various +glands and organs of the digestive system in chronic appendicitis. +It readily explains also the extraordinary improvement in the digestive +functions and the general health which follows the removal +of an appendix which is so slightly altered physically that only +the clinical results could persuade one that this slight change could +be an adequate cause for such far-reaching and important symptoms. +This hypothesis explains certain gall-bladder phenomena likewise,-- +indigestion, loss of weight, disturbed functions, etc.,--and it +may supply the explanation of the disturbance caused by an active +anal fissure, which is a potent noci-associator, and the consequent +disproportionate relief after the trivial operation for its cure. +Noci-association would well explain also the great functional disturbances +of the viscera which immediately follow abdominal operations. + +Postoperative and traumatic neuroses are at once explained on +the ground of noci-association, the resulting strain from which, +upon the brain-cells, causes in them physical lesions. +If one were placed against a wall and were looking into the gun muzzles +of a squad of soldiers, and were told that there were nine chances +out of ten that he would not be killed outright when the volley +was fired, would it help him to be told that he must not be afraid? +Such an experience would be written indelibly on his brain. +This corresponds closely to the position in which some surgical patients +are placed. In railway wrecks, we can readily understand the striking +difference between the after-effects in the passengers who were conscious +at the time of the accident and those who were asleep or drunk. +In the latter the noci-perceptors and receptors were not aroused, +hence their immunity to the nervous shock. In the functional disturbances +of the pelvic organs, association and summation may play a large role. +On this hypothesis many cases of neurasthenia may well be explained. +From the behavior of the individual as a whole we may well conclude +that summation is but a scientific expression for "nagging." +Many other pathologic phenomena may be explained in a similar manner. +Thus we can understand the variations in the gastric analyses in a +timid patient alarmed over his condition and afraid of the hospital. +He is integrated by fear, and as fear takes precedence over all +other impulses, no organ functionates normally. For the same reason, +one sees animals in captivity pine away under the dominance of fear. +The exposure of a sensitive brain to the naked possibility of death from +a surgical operation may be compared to uncovering a photographic plate +in the bright sunlight to inspect it before putting it in the camera. +This principle explains, too, the physical influence of the physician +or surgeon, who, by his PERSONALITY, inspires, like a Kocher, +absolute confidence in his patient. The brain, through its power +of phylogenetic association, controls many processes that have wholly +escaped from the notice of the "practical man." It is in accordance +with the law of association that a flower, a word, a touch, a cool breeze, +or even the thought of a fishing rod or of a gun, is helpful. +On the contrary, all suggestions of despair or misfortune-- +a corrugated brow, the gloomy silence of despair, or a doubtful word-- +are equally depressing. In like manner, one could add many +illustrations of the symbolism that governs our daily lives. +Thus we see that through the laws of inheritance and noci-association, +we are able to read a new meaning into the clinical phenomena +of various diseases. + + +Observations on Patients whose Associational Centers are Dulled, +and on Diseases and Injuries of Regions not Endowed with Nociceptors + + +Reversing the order of our reasoning, let us now glance at the patient +who is unconscious and who, therefore, has lost much of the power +of association. His mouth is usually dry, the digestive processes +are at a low ebb, the aroma of food causes no secretion of saliva, +tickling the nose causes no sneezing; he catches no cold. +The laryngeal reflex is lost and food may be quietly inhaled; +the entire process of metabolism is low. The contrast between a man +whose associational centers are keen and a man in whom these centers +are dulled or lost is the contrast between life and death. + +In accordance with the law of adaptation through natural selection, +phylogeny, and association, one would expect no pain in abscess +of the brain, in abscess of the liver, in pylephlebitis, +in infection of the hepatic vessels, in endocarditis. +This law explains why there are no nociceptors for cancer, +while there are active nociceptors for the acute infections. +It is because nature has no helpful response to offer against cancer, +while in certain of the acute pyogenic infections the nociceptors +force the beneficent physiologic rest. + +Could we dispossess ourselves of the shackles of psychology, +forget its confusing nomenclature, and view the human brain, +as Sherrington has said, "as the organ of, and for the adaptation +of nervous reaction," many clinical phenomena would appear in +a clearer light. + + +Natural Selection and Chemical Noci-association in the Infections + + +Thus far we have considered the behavior of the individual as a whole +in his response to a certain type of noci-influences. We have been voicing +our argument in terms of physical escape from GROSS physical dangers, +or of grappling with GROSS NERVE-MUSCULAR enemies of the same or of +other species. To explain these phenomena we have invoked the aid +of the laws of natural selection and phylogenetic association. +If our conclusions be correct, then it should follow that in the same +laws we may find the explanation of immunity, which, of course, +means a defensive response to our MICROSCOPIC enemies. There should +be no more difficulty in evolving an efficient army of phagocytes +by natural selection, or in developing specific chemical reactions +against _*microscopic enemies_, than there was in evolving the various +nociceptors for our nerve-muscular defense against our _*gross enemies_. +That immunity is a chemical reaction is no argument against +the application of the law of natural selection or of association. +What essential difference is there between the chemical defense of +the skunk against its NERVE-MUSCULAR enemies and its chemical defense +(immunity) against its MICROSCOPIC ENEMIES? + +The administration of vaccines becomes the adequate stimulus which +awakens phylogenetic association of a chemical nature as a result +of which immune bodies are produced. + +In discussing this subject I will raise only the question whether +or not the specific character of the inaugural symptoms of some +infectious diseases may be due to phylogenetic association. +These inaugural symptoms are measurably a recapitulation of the leading +phenomena of the disease in its completed clinical picture. +Thus, the furious initiative symptoms of pneumonia, of peritonitis, +or erysipelas, of the exanthemata, are exaggerations of phenomena +which are analogous to the phenomena accompanying physical injury +and fear of physical violence. Just as the acute phenomena of fear, +or those which accompany the adequate stimulation of nociceptors, +are recapitulations of phylogenetic struggles, so may the inaugural +symptoms of an infection be a similar phylogenetic recapitulation +of the course of the disease. A certain amount of negative +evidence is supplied by a comparison of the response to a dose +of toxins with the response to a dose of a standard drug. +No drug in therapeutic dosage except the iodin compounds causes +a febrile response; no drug causes a chill; on the other hand, +all specific toxins cause febrile responses and many cause chills. +If a species of animal had been poisoned by a drug during vast periods +of time, and if natural selection had successfully established +a self-defensive response, then the administration of that drug would +cause a noci-association (chemical), and a specific reaction analogous +to that following the administration of Coley's toxins might be expected. +Bacterial noci-association probably operates through the same +law as that through which physical noci-association operates. +Natural selection is impartial, however. It must be supposed that it +acts impartially upon the microscopic invader and upon the host. +On this ground one must infer that, in accordance with the same law +of natural selection, the bacteria of acute infections have met +by natural selection each advance in the struggle of the host +for immunity. Hence the fast and furious struggle between man +and his microscopic enemies merely indicates to what extent natural +selection has developed the ATTACK and the DEFENSE respectively. +This struggle is analogous to the quick and decisive battles +of the carnivora when fighting among themselves or when contending +against their ancient enemies. But when phylogenetically strange +animals meet each other, they do not understand how to conduct a fight: +natural selection has not had the opportunity of teaching them. +The acute infections have the characteristics of being ancient enemies. +On this hypothesis one can understand the high mortality of measles +when it is introduced into a new country. By natural selection, +measles has become a powerful enemy of the human race, and a race +to which this infection is newly introduced has not had the advantage +of building up a defense against it by the law of natural selection. +May not the phenomena of anaphylaxis be studied on associational lines? +Then, too, there may be chemical noci-associations with enemies +now extinct, which, like the ticklish points, may still be active +on adequate stimulation. This brief reference to the possible +relation of the phenomena of the acute infections to the laws +of natural selection and of specific chemical noci-association has +been made as a suggestion. Since the doctrine of evolution explains +all or nothing, I have included many phenomena to see how reasonable +or unreasonable such an explanation might be. + + +Recapitulation + + +The following are the principal points presented: In operations +under inhalation anesthesia the nerve impulses from the trauma +reach every part of the brain--the cerebrum that is apparently +anesthetized as well as the medulla that is known to remain awake-- +the proof being the PHYSIOLOGIC exhaustion of and the PATHOLOGIC +change in the nerve-cells. Under ether anesthesia the damage +to the nerve-cells is at least four times greater than under +nitrous oxid. Inhalation anesthesia is, therefore, but a veneer-- +a mask that "covers the deep suffering of the patient." The cause +of the exhaustion of the brain is the discharge of nervous energy +in a futile effort to energize the paralyzed muscles in an attempt +to escape from the injury just as if no anesthetic had been given. +The exhaustion is, therefore, of the same nature as that from overexertion, +but if the nerve-paths connecting the field of operation +and the brain be blocked, then there is no discharge of nervous +energy from the trauma, and consequently there is no exhaustion, +however severe or prolonged the operation may be. + +Fear is a factor in many injuries and operations. The phenomena +of fear probably are exhibited only by animals whose natural defense +is nerve-muscular. The skunk, the porcupine, the turtle, have little +or no fear. Fear is born of the innumerable injuries which have +been inflicted in the course of evolution. Fear, like trauma, +may cause physiologic exhaustion of and morphologic changes +in the brain-cells. The representation of injury, which is fear, +being elicited by phylogenetic association, may be prevented +by the exclusion of the noci-association or by the administration +of drugs like morphin and scopolamin, which so impair the associational +function of the brain-cells that immunity to fear is established. +Animals whose natural defense is in muscular exertion, among which is man, +may have their dischargeable nervous energy exhausted by fear alone, +or by trauma alone, but most effectively by the combination of both. +What is the mechanism of this discharge of energy? It is the adequate +stimulation of the nociceptors and the physiologic response for the purpose +of self-preservation. According to Sherrington, the nervous system +responds in action as a whole and to but one stimulus at a time. +The integration of the individual as a whole occurs not alone in injury +and fear, but also, though not so markedly, as a result of other +phylogenetic associations, such as those of the chase and procreation. +When adequate stimuli are repeated with such rapidity that the new +stimulus is received before the effect of the previous one has +worn off, a higher maximum effect is produced than is possible +under a single stimulus, however powerful. + +Sexual receptors are implanted in the body by natural selection, +and the adequate stimuli excite the nerve-muscular reactions +of conjugation in a manner analogous to the action of the adequate +stimuli of the nociceptors. The specific response of either +the sexual receptors or the nociceptors is at the expense +of the total amount of nervous energy available at the moment. +Likewise in daily labor, which, in the language of evolution, +is the chase, nervous energy is expended. Under the dominance +of fear or injury, however, the integration is most nearly +absolute and probably every expenditure of nervous energy which is +not required for efforts toward self-preservation is arrested; +hence fear and injury drain the cup of energy to the dregs. +This is the potential difference between fear and desire, +between injury and conjugation. + +What is the practical application of this? In operative surgery +there is introduced a new principle, which removes from surgery much +of the immediate risk from its trauma by establishing ANOCI-ASSOCIATION; +it places certain of the phenomena of fear on a physical basis; +it explains to us the physical basis for the impairment of the entire +individual under worry or misfortune; it makes evident the physical +results of the daily noci-associations experienced by the individual +as a social unit. On the other hand, it explains the power +of therapeutic suggestion and of other influences which serve +for the time to change the noci-integration; it shows the physical +basis for the difference between hope and despair; it explains +some of the phenomena of Graves' disease, of sexual neurasthenia, +possibly of hay-fever and of the common cold. The principle is probably +equally applicable to the acute infections, in each of which chemical +noci-association gives rise to many of the phenomena of the disease +and it explains their cure by natural immunity and by vaccines. +This hypothesis should teach us to view our patients as a whole; +and especially should it teach the surgeon gentleness. It should +teach us that there is something more in surgery than mechanics, +and something more in medicine than physical diagnosis and drugs. + + +Conclusion + + +The brain-cells have existed for eons and, amid the vicissitudes +of change, they have persisted with perhaps less alteration than has +the crust of the earth. Whether in man or in the lower animals, +they are related to and obey the same general biologic laws, +thus being bound to the entire past and performing their function +in accordance with the law of phylogenetic association. + +For so long a time have we directed our attention to tumors, +infections, and injuries that we have not sufficiently considered +the vital force itself. We have viewed each anatomic and pathologic +part as an entity and man as an isolated phenomenon in nature. +May we not find in the laws of adaptation under natural selection, +and of phylogenetic association, the master key that will disclose +to us the explanation of many pathologic phenomena as they have +already explained many normal phenomena? + +And may medicine not correlate the pathologic phenomena of the sick +man with the forces of evolution, as the naturalists have correlated +the phenomena of the sound man, and thus may not disease, as well +as health, be given its evolutionary setting? + + + +PHYLOGENETIC ASSOCIATION IN RELATION TO THE EMOTIONS[*] + + +[*] Address before the American Philosophical Society, Philadelphia, +April 22, 1911. + + +The surgeon is familiar with the manifestations of every variety +of the human emotions in the various stations of life, from infancy +to senility, in health and in disease. Not only does he come +into intimate contact with the emotions displayed by the victims +of disease and of accidents, but he also observes those manifested +by the relatives and friends of the families of his patients. +Moreover, he is unhappily forced to notice the emotional effect +upon himself when he is waging an unequal battle against death-- +the strain and worry at a crisis, when a life is in the balance +and a single false move may be fatal, is an experience known only +to the operating surgeon. + +For the data for this paper, therefore, in which I shall for the most +part limit my discussion to the strongest of all emotions--FEAR--I have +drawn largely from my personal experience as a surgeon, as well +as from an experimental research in which I have had the valuable +assistance of my associates, Dr. H. G. Sloan, Dr. J. B. Austin, +and Dr. M. L. Menten. + +I believe it can be shown that it is possible to elicit the emotion +of fear only in those animals that utilize a motor mechanism +in defense against danger or in escape from it. For example, +the defense of the skunk is a diabolic odor which repels its enemies; +the skunk has no adequate equipment for defense or escape by +muscular exertion, and the skunk therefore shows little or no fear. +Again, certain species of snakes are protected by venom; +they possess no other means of defense nor have they adequate +motor mechanisms for escape and they show no fear. Because of +their strength other animals, such as the lion, the grizzly bear, +and the elephant, show but little fear (Fig. 6). Animals which have +an armored protection, such as the turtle, show little fear. +It is, therefore, obvious that fear is not universal and that the +emotion of fear is felt only by those animals whose self-preservation +is dependent upon an uncertain adequacy of their power of muscular +exertion either for defense or for flight (Fig. 7). + +What are the principal phenomena of fear? They are palpitation +of the heart, acceleration of the rate and alteration of the rhythm +of the respiration, cold sweat, rise in body temperature, +tremor, pallor, erection of the hair, suspension of the principal +functions of digestion, muscular relaxation, and staring of the eyes +(Fig. 12). The functions of the brain are wholly suspended except those +which relate to the self-protective response against the feared object. +Neither the brain nor any other organ of the body can respond +to any other lesser stimulus during the dominance of fear. + +From these premises it would appear that under the influence +of fear, most, perhaps all, of the organs of the body are divided +sharply into two classes: First, those that are stimulated, +and, second, those that are inhibited. Those that are stimulated +are the entire muscular system, the vasomotor and locomotor systems, +the senses of perception, the respiration, the mechanism for erecting +the hair, the sweat-glands, the thyroid gland, the adrenal gland +(Cannon), and the special senses. On the other hand, +all the digestive and procreative functions are inhibited. +What is the significance of this stimulation of some and inhibition +of other organs? As far as we know, the stimulated organs +increase the efficiency of the animal for fight or for flight. +It is through skeletal muscles that the physical attack or escape +is effected; these muscles alone energize the claws, the teeth, +the hoofs, and the means for flight. The increased action of the +muscles of the heart and the blood-vessels increases the efficiency +of the circulation; the secretion of the adrenal gland causes a rise +in the blood-pressure; the increased action of the thyroid gland causes +an increased metabolic activity; there is evidence that glycogen +is actively called out, this being the most immediately available +substance for the production of energy; the increased activity +of the respiration is needed to supply the greater need of oxygen +and the elimination of the increased amount of waste products; +the dilatation of the nostrils affords a freer intake of air; +the increased activity of the sweat-glands is needed to regulate +the temperature of the body which the increased metabolism causes to rise. +The activity of all the organs of perception--sight, hearing, smell-- +is increased in order that the danger may be more accurately perceived. +It cannot be a mere coincidence that the organs and the tissues +that are stimulated in the emotion of fear are precisely those that +are actually utilized in a physical struggle for self-preservation. + +Are any other organs stimulated by fear except those that can +or that do assist in making a defensive struggle? I know of none. +On the other hand, if an animal could dispense with his bulky +digestive organs, whose functions are suspended by fear, if he could, +so to speak, clear his decks for battle, it would be to his advantage. +Although the marvelous versatility of natural selection apparently +could devise no means of affording this advantage, it nevertheless shut +off the nervous current and saved the vital force which is ordinarily +consumed by these non-combatants in the performance of their functions. +Whatever may be the origin of fear, its phenomena are due to a +stimulation of all the organs and tissues that add to the efficiency +of the physical struggle for self-preservation and an inhibition +of the func- + + +{illust. caption = FIG. 19--THE BROAD JUMP. Note the similarity +of the expression to the facial expression of fear and of anger +(Figs. 12 and 21). (Wm. J. Brownlow, drawn from photo.) +tions of the leading organs that do not participate in that struggle-- +the non-combatants, so to speak. Fear arose from injury, +and is one of the oldest and surely the strongest emotion. +By the slow process of vast empiricism nature has evolved the +wonderful defensive motor me-chanism of many animals and of man. +The stimulation of this mechanism leading to a physical struggle is action, +and the stimulation of this mechanism without action is emotion. +We may say, therefore, that fear is a PHYLOGENETIC FIGHT OR FLIGHT (Fig. +18). On this hypothesis all the organs and parts {illust. caption += FIG. 20.-FINISH OF RELAY RACE. + +Compare the facial expression of the runners with those in Figs. +12, 19, 22. These pictures illustrate the fact that the same +mechanism is stimulated in emotion as in physical action. +(Photo by Underwood and Underwood, N. Y.)} + + +of the body are integrated, connected, or correlated for the +self-preservation of the individual by the activity of his motor mechanism +(Figs. 12, 19, and 20). We fear not in our hearts alone, not in our +brains alone, not in our viscera alone--fear influences every organ +and tissue; each organ or tissue is stimulated or inhibited according +to its use or hindrance in the physical struggle for existence. +By thus concentrating all or most of the nerve force on the nerve-muscular +mechanism for defense, a greater physical power is developed. +Hence it is that under the stimulus of fear animals are able to perform +preternatural feats of strength. For the same reason, the exhaustion +following fear will be increased as the powerful stimulus of fear drains +the cup of nervous energy even though no visible action may result. +An animal under the stimulus of fear may be likened to an automobile +with the clutch thrown out but whose engine is racing at full speed. +The gasoline is being consumed, the machinery is being worn, +but the machine as a whole does not move, though the power of its +engine may cause it to tremble. + +When this conception is applied to the human beings of today, +certain mysterious phenomena are at once elucidated. It must be borne +in mind that man has not been presented with any new organs to meet +the requirements of his present state of civilization; indeed, not only +does he possess organs of the same type as those of his savage fellows, +but of the same type also as those possessed by the lower animals even. +In fact, man has reached his present status of civilization with +the primary equipment of brutish organs. Perhaps the most striking +difference between man and animals lies in the greater control +which man has gained over his primitive instinctive reactions. +As compared with the entire duration of organic evolution, +man came down from his arboreal abode and assumed his new role +of increased domination over the physical world but a moment ago. +And now, though sitting at his desk in command of the complicated +machinery of civilization, when he fears a business catastrophe +his fear is manifested in the terms of his ancestral physical battle +in the struggle for existence. He cannot fear intellectually, +he cannot fear dispassionately, he fears with all his organs, +and the same organs are stimulated and inhibited as if, instead of it +being a battle of credit, of position, or of honor, it were a physical +battle with teeth and claws. Whether the cause of acute fear +be moral, financial, social, or stage fright, the heart beats wildly, +the respirations are accelerated, perspiration is increased, +there are pallor, trembling, indigestion, dry mouth, etc. +The phenomena are those which accompany physical exertion +in self-defense or escape. There is not one group of phenomena +for the acute fear of the president of a bank in a financial +crash and another for the hitherto trusted official who suddenly +and unexpectedly faces the imminent probability of the penitentiary; +or one for a patient who unexpectedly finds he has a cancer +and another for the hunter when he shoots his first big game. +Nature has but one means of response to fear, and whatever its cause +the phenomena are always the same--always physical. + +If the stimulus of fear be repeated from day to day, whether in +the case of a mother anxious on account of the illness of a child; +a business man struggling against failure; a politician under contest +for appointment; a broker in the daily hazard of his fortune; +litigants in legal battle, or a jealous lover who fears a rival; +the countless real as well as the baseless fears in daily life, +in fact, all forms of fear, as it seems to me, express themselves +in like terms of ancestral physical contests. On this law, +fear dominates the various organs and parts of the body. + +Anger and fear express opposite emotional states. Fear is the +expression of a strong desire to escape from danger; anger, of a +strong desire to attack physically and to vanquish opposition. +This hypothesis is strongly supported by the outward expressions +of fear and of anger. When the business man is conducting a struggle +for existence against his rivals, and when the contest is at +its height, he may clench his fists, pound the table, perhaps show +his teeth, and exhibit every expression of physical combat. +Fixing the jaw and showing the teeth in anger merely emphasize +the remarkable tenacity of phylogeny. Although the development +of the wonderful efficiency of the hands has led to a modification +of the once powerful canines of our progenitors, the ancestral use +of the teeth for attack and defense is attested in the display of anger. +In all stations of life differences of opinion may lead to argument +and argument to physical combats, even to the point of killing. +The physical violence of the savage and of the brute still lies +surprisingly near the surface (Fig. 21). + +We have now presented some of the reasons based largely on gross animal +behavior why fear is to be regarded as a response to phylogenetic +association with physical danger. In further support of this hypothesis, +I shall now present some clinical and experimental evidence. +Although there is not convincing proof, yet there is evidence that +the effect of the stimulus of fear upon the body when unaccompanied +by physical activity is more injurious than is an actual physical +contest which results in fatigue without gross physical injury. +It is well known that the soldier who, while under fire, +waits in vain for orders to charge, suffers more than the soldier +who flings himself into the fray; and that a wild animal endeavoring +to avoid capture suffers less than one cowering in captivity. +An unexpressed smouldering emotion is measurably relieved by action. +It is probable that the various energizing substances needed in +physical combat, such as the secretions of the thyroid, the adrenals +(Cannon), etc., may cause physical injury to the body when they +are not consumed by action (Fig. 22). + +That the brain is definitely influenced--damaged even-- +by fear has been proved by the following experiments: +Rabbits were frightened by a dog but were neither injured nor chased. +After various periods of time the animals were killed and their +brain-cells compared with the brain-cells of normal animals-- +wide-spread changes were seen (Fig. 13). The principal clinical phenomena +expressed by the rabbit were rapid heart, accelerated respiration, +prostration, tremors, and a rise in temperature. The dog showed +similar phenomena, excepting that, instead of such muscular relaxation +as was shown by the rabbit, it exhibited aggressive muscular action. +Both the dog and the rabbit were exhausted but, although the dog +exerted himself actively and the rabbit remained physically passive, +the rabbit was much more exhausted. + +Further observations were made upon the brain of a fox +which had been chased for two hours by members of a hunt club, +and had been finally overtaken by the hounds and killed. +Most of the brain-cells of this fox, as compared with those of a +normal fox, showed extensive physical changes (Fig. 4). + +The next line of evidence is offered with some reservation, +but it has seemed to me to be more than mere idle speculation. +It relates to the phenomena of one of the most interesting diseases +in the entire category of human ailments--I refer to exophthalmic goiter, +or Graves' disease, a disease primarily involving the emotions. +This disease is frequently the direct sequence of severe +mental shock or of a long and intensely worrying strain. +The following case is typical: A broker was in his usual health up +to the panic of 1907; during this panic his fortune and that of others +were for almost a year in jeopardy, failure finally occurring. +During this heavy strain he became increasingly nervous and by +imperceptible degrees there developed a pulsating enlargement of +the thyroid gland, an increased prominence of the eyes, marked increase +in perspiration--profuse sweating even--palpitation of the heart, +increased respiration with frequent sighing, increase in blood-pressure; +there were tremor of many muscles, rapid loss of weight and strength, +frequent gastro-intestinal disturbances, loss of normal control +of his emotions, and marked impairment of his mental faculties. +He was as completely broken in health as in fortune. +These phenomena resembled closely those of fear and followed +in the wake of a strain which was due to fear. + +In young women exophthalmic goiter often follows in the wake +of a disappointment in love; in women, too, it frequently follows +the illnesses of children or parents during which they have had +to endure the double strain of worry and of constant care. +Since such strains usually fall most heavily upon women, they are +the most frequent victims of this disease. Now, whatever the exciting +cause of exophthalmic goiter, whether it be unusual business worry, +disappointment in love, a tragedy, or the illness of a loved one, +the symptoms are alike and closely resemble the phenomena of one +of the great primitive emotions. How could disappointment in love +play a role in the causation of Graves' disease? If the hypothesis +which has been presented as an explanation of the genesis and +the phenomena of fear be correct, then that hypothesis explains +also the emotion of love. If fear be a phylogenetic physical +defense or escape which does not result in muscular action, +then love is a phylogenetic conjugation without physical action. +The quickened pulse, the leaping heart, the accelerated respiration, +the sighing, the glowing eye, the crimson cheek, and many other +phenomena are merely phylogenetic recapitulations of ancestral acts. +The thyroid gland is believed to participate in such physical activities. +Hence it may well follow that the disappointed maiden who is intensely +integrated for a youth will, at every thought of him, be subjected +by phylogenetic association to a specific stimulation analogous +to that which attended the ancestral consummation. Moreover, a happy +marriage has many times been followed by a cure of the exophthalmic +goiter which appeared in the wake of such an experience. + +The victims of Graves' disease present a counterpart of +emotional exhaustion. That the emotions in Graves' disease are +abnormally acute is illustrated by my personal observation +of the death of a subject of this disease from fear alone. +Whatever the exciting cause of this disease, the symptoms are the same; +just as in fear, the phenomena are the same whatever the exciting cause. + +Figures 12 and 16 show the resemblance between the outward appearances +of a patient with Graves' disease and of a person obsessed by fear. +Fear and Graves' disease have the following phenomena in common: +Increased heart-beat, increased respiration, rising temperature, +muscular tremors, protruding eyes, loss in weight; Cannon has found +an increased amount of adrenalin in the blood in fear and Frankel +in Graves' disease; increased blood-pressure; muscular weakness; +digestive disturbances; impaired nervous control; hypersusceptibility +to stimuli; in protracted intense fear the brain-cells show marked +physical changes, and in Graves' disease analogous changes are seen +(Figs. 13 C and 15). In Graves' disease there seems to be a composite +picture of an intense expression of the great primitive emotions. +If Graves' disease be a disease of the great primitive emotions, +or rather of the whole motor mechanism, how is the constant flow +of stimulation of this complicated mechanism supplied? It would +seem that there must be secreted in excessive amount some substance +that activates the motor mechanism. The nervous system in Graves' +disease is hypersusceptible to stimuli and to thyroid extract. +It might follow that even a normal amount of thyroid secretion would +lead to excessive stimulation of the hypersusceptible motor mechanism. + +This condition of excessive motor activity and hyperexcitability may +endure for years. What is the source of this pathologic excitation? +The following facts may give a clue. In suitable cases of Graves' +disease, if the thyroid secretion is sufficiently diminished by a removal +of a part of the gland or by interrupting the nerve and the blood supply, +the phenomena of the disease are diminished immediately, and in favorable +cases the patient is restored to approximately the normal condition. +The heart action slows, the respiratory rate falls, the restlessness +diminishes, digestive disturbances disappear, tremors decrease, +there is a rapid increase in the body weight, and the patient gradually +resumes his normal state. On the other hand, if for a period +of time extract of the thyroid gland is administered to a normal +individual in excessive dosage, there will develop nervousness, +palpitation of the heart, sweating, loss of weight, slight protrusion +of the eyes, indigestion; in short, most of the phenomena of Graves' +disease and of the strong emotions will be produced artificially +(Figs. 15 and 23). When the administration of the thyroid extract +is discontinued, these phenomena may disappear. On the other hand, +when there is too little or no thyroid gland, the individual +becomes dull, stupid, and emotionless, though he may be irritable; +while if a sufficient amount of thyroid extract be given to such +a patient he may be brought back to his normal condition. + +Hence we see that the phenomena of the emotions may within certain +limits be increased, diminished, or abolished by increasing, +diminishing, or totally excluding the secretion of the thyroid gland. + +Graves' disease may be increased by giving thyroid extract and by fear. +It may be diminished by removing a part of the gland, or by +interrupting the blood and nerve supply, or by complete rest. +In addition, at some stage of Graves' disease there is an +increase in the size and in the number of the secreting cells. +These facts regarding the normal and the pathologic supply of thyroid +secretion point to this gland as one of the sources of the energizing +substance or substances, by means of which the motor phenomena +of animals are executed and their emotions expressed. + +Anger is similar to fear in origin and, like fear, is an integration +and stimulation of the motor mechanism and its accessories. +Animals which have no natural weapons for attack experience neither +fear nor anger, while the animals which have weapons for attack +express anger principally by energizing the muscles used in attack. +Although, as has already been stated, the efficiency of the hands +of man has largely supplanted the use of the teeth, he still shows +his teeth in anger and so gives support to the theory that this +emotion is of remote ancestral origin and proves the great persistence +of phylogenetic association. On this conception we can understand +why it is that a patient consumed by worry--which to me signifies +interrupted stimulation, a state of alternation between hope +and fear--suffers so many bodily impairments and diseases even. +This hypothesis explains the slow dying of animals in captivity. +It explains the grave digestive and metabolic disturbances which +appear under any nerve strain, especially under the strain of fear, +and the great benefits of confidence and hope; it explains the nervousness, +loss of weight, indigestion--in short, the comprehensive physical +changes that are wrought by fear and by sexual love and hate. +On this hypothesis we can understand the physical influence +of one individual over the body and personality of another; +and of the infinite factors in environment that, through phylogenetic +association, play a role in the functions of many of our organs. +It is because under the uncompromising law of survival of the fittest +we were evolved as motor beings that we do not possess any organs or +faculties which have not served our progenitors in accomplishing their +survival in the relentless struggle of organic forms with one another. +We are now, as we were then, essentially motor beings, and the only way in +which we can meet the dangers in our environment is by a motor response. +Such a motor response implies the integration of our entire being +for action, this integration involving the activity of certain glands, +such as the adrenals (Cannon), the thyroid, the liver, etc., which throw +into the blood-stream substances which help to form energy, but which, +if no muscular action ensues, are harmful elements in the blood. +While this motor preparation is going on, the entire digestive +tract is inhibited. It thus becomes clear why an emotion is more +harmful than action. + +Any agency that can sufficiently inspire faith,--dispel worry,-- +whether that agency be mystical, human, or divine, will at once +stop the body-wide stimulations and inhibitions which cause +lesions which are as truly physical as is a fracture. +The striking benefits of good luck, success, and happiness; +of a change of scene; of hunting and fishing; of optimistic +and helpful friends, are at once explained by this hypothesis. +One can also understand the difference between the broken body +and spirits of an animal in captivity and its buoyant return to its +normal condition when freed. + +But time will not permit me to follow this tempting lead, which has +been introduced for another purpose--the proposal of a remedy. + +Worries either are or are not groundless. Of those that have +a basis, many are exaggerated. It has occurred to me to utilize +as an antidote an appeal to the same great law that originally +excited the instinctive involuntary reaction known as fear-- +the law of self-preservation. + +I have found that if an intelligent patient who is suffering from +fear can be made to see so plainly as to become firmly convinced +that his brain, his various organs, indeed his whole being, +could be physically damaged by fear, that this same instinct of +self-preservation will, to the extent of his conviction, banish fear. +It is hurling a threatened active militant danger, whose injurious +influences are both certain and known, against an uncertain, +perhaps a fancied, one. In other words, fear itself is an injury +which when recognized is instinctively avoided. In a similar manner +anger may be softened or banished by an appeal to the stronger +self-preserving instinct aroused by the fear of physical damage, +such as the physical injury of brain-cells. This playing of one +primitive instinct against another is comparable to the effect +produced upon two men who are quarreling when a more powerful enemy +of both comes threateningly on the scene. + +The acute fear of a surgical operation may be banished by the use +of certain drugs that depress the associational power of the brain and +so minimize the effect of the preparations that usually inspire fear. +If, in addition, the entire field of operation is blocked by local +anesthesia so that the associational centers are not awakened, +the patient will pass through the operation unscathed. + +The phylogenetic origin of fear is injury, hence injury and fear cause +the same phenomena. In their quality and in their phenomena psychic +shock and traumatic shock are the same. The perception of danger +by the special senses in the sound of the opening gun of a battle, +or in the sight of a venomous snake, is phylogenetically the same +and causes the same effects upon the entire body as an operation under +anesthesia or a physical combat in that each drives the motor mechanism. +The use of local anesthetics in the operative field prevents +nerve-currents from the seat of injury from reaching the brain and there +integrating the entire body for a self-defensive struggle. The result, +even though a part of the brain is asleep and the muscles paralyzed, +is the same as that produced by the interception of the terrifying +sound of the gun, or of the sight of the dangerous reptile, +since the stimulation of the motor mechanism is prevented. + +By both the positive and the negative evidence we are forced +to believe that the emotions are primitive instinctive reactions +which represent ancestral acts; and that they therefore utilize +the complicated motor mechanism which has been developed by the forces +of evolution as that best adapted to fit the individual for his +struggle with his environment or for procreation. + +The mechanism by which the motor acts are performed and the mechanism +by which the emotions are expressed are one and the same. +These acts in their infinite complexity are suggested by association-- +phylogenetic association. When our progenitors came in contact +with any exciting element in their environment, action ensued then +and there. There was much action--little restraint or emotion. +Civilized man is really in auto-captivity. He is subjected +to innumerable stimulations, but custom and convention frequently +prevent physical action. When these stimulations are sufficiently +strong but no action ensues, the reaction constitutes an emotion. +A phylogenetic fight is anger; a phylogenetic flight is fear; +a phylogenetic copulation is sexual love, and so one finds in this +conception an underlying principle which may be the key to an +understanding of the emotions and of certain diseases. + + + +PAIN, LAUGHTER, AND CRYING[*] + +[*] Address delivered before the John Ashhurst, Jr.. Surgical Society +of the University of Pennsylvania, May 3, 1912. + +PAIN + + +Pain, like other phenomena, was probably evolved for a particular purpose-- +surely for the good of the individual; like fear and worry, +it frequently is injurious. What then may be its purpose? + +We postulate that pain is one of the phenomena which result +from a stimulation to motor action. When a barefoot boy steps +on a sharp stone it is important that the injuring contact be +released as quickly as possible; and therefore physical injury pain +results and impels the required action. Anemia of the soft parts +at the points of pressure results from prolonged sitting or lying +in one position, and as a result pain compels a muscular action +that shifts the damaging pressure--this is the pain of anemia; +when the rays of the blazing sun shine directly upon the retina, +pain immediately causes a protective muscular action--the lid is closed, +the head turns away--this is light pain; when standing too close +to a blazing fire the excessive heat causes a pain which results +in the protective muscular action of moving away--this is heat pain; +when the urinary bladder is acutely overdistended the resultant +pain induces voluntary as well as involuntary muscular contraction-- +this is evacuation pain; associated with defecation is a characteristic +warning pain, and an active pain which induces the required +muscular action--this, like the pain accompanying micturition, +is an evacuation pain; in obstruction of the urinary passages +and of the large and the small intestine the pain is exaggerated, +as is the accompanying muscular contraction--this is a pathologic +evacuation pain; when the fetus reaches full term and labor is +to begin, it is heralded by pain which is associated with rhythmic +contractions of the uterine muscle; later, many other muscles +take part in the birth and pain is associated with all these +muscular contractions--these are labor pains; when a foreign body, +be it ever so small, falls upon the conjunctiva or cornea there +results what is perhaps the acutest pain known, and quick and active +muscular action follows--this is special contact pain. Special pain +receptors are placed in certain parts of the nose, the pharynx, +and the larynx, the stimulation of which causes special motor acts, +such as sneezing, hawking, coughing. Curiously vague pains are +associated with the protective motor act of vomiting and with the sexual +motor acts--these may be termed nausea pains and pleasure pains. +We now see, therefore, that against the injurious physical contacts +of environment, against heat and cold, against damaging sunlight, +against local anemia when resting or sleeping, the body is protected +by virtue of the muscular action which results from pain. +Then, too, for the emptying of the pregnant uterus, for the evacuation +of the intestine and of the urinary bladder as normal acts, +and for the overcoming of obstructions in these tracts, +pain compels the required muscular actions, For passing gall-stones +and urinary calculi, urgent motor stimuli are awakened by pain. +For each of these diversified pains the consequent muscular action +is specific in type, distribution, and intensity. This statement +is so commonplace that we are apt to miss the significance and +the wonder of it. It is probable that every nerve-ending in the skin +and every type of stimulation represents a separate motor pattern, +the adequate stimulation of which causes always the same response. + +Let us pass on to the discussion of another and perhaps even +more interesting type of pain, that associated with infection. +Not all kinds of infection are painful; and in those infections +that may be associated with pain there is pain only when certain +regions of the body are involved. Among the infections that are not +associated with pain are scarlet fever, typhoid fever, measles, malaria, +whooping-cough, typhus fever, and syphilis in its early stages. +The infections that are usually, though not always, associated with +pain are the pyogenic infections. The pyogenic infections +and the exanthemata constitute the great majority of infections +and are the basis of the discussion which follows. + +I will state one of my principal conclusions first, _i. +e_., that the only types of infection that are associated with pain +are those in which the infection may be spread by muscular action +or those in which the fixation of parts by continued muscular +rigidity is an advantage; and, further, as a striking corollary, +that the type of infection that may cause muscular action when it +attacks one region of the body may cause no such action when it +attacks another region. + +The primary, and perhaps the most striking, difference between +the painless exanthemata and the painful pyogenic infections is that +in the case of the exanthemata the protective response of the body +is a chemical one,--the formation of antibodies in the blood, +which usually produce permanent immunity,--while the response to the +pyogenic infections is largely phagocytic. In the pyogenic infections, +in order to protect the remainder of the body, which, of course, +enjoys no immunity, every possible barrier against the spread +of the infection is thrown about the local point of infection. +How are these barriers formed? First, lymph is poured out, then the part +is fixed by the continuous contraction of the neighboring muscles +and by the inhibition of those muscles that, in the course of their +ordinary function, would by their contractions spread the infection. +Wherever there is protective muscular rigidity there is also pain. +On the other hand, in pyogenic infections in the substance +of the liver, in the substance of the kidney, within the brain, +in the retroperitoneal space, in the lobes of the lung, in the chambers +of the heart and in the blood-vessels of the chest and the abdomen, +in all locations in which muscular contractions can in no way assist +in localizing the disease, pyogenic infections produce no muscular +rigidity and no pain. Apparently, therefore, only those infections are +painful which are associated with a protective muscular contraction. +This explains why tuberculosis of the hip is painful, while tuberculosis +of the lung is painless. + +There is a third type of pain which modifies muscular action +in a curious way. We have already stated that local pain serves +an adaptive purpose. In this light let us now consider headache. +Headache is one of the commonest initiatory symptoms of the +various infections, especially of those infections which are +accompanied by no local pain and by no local muscular action. +In peritonitis, cholecystitis, pleurisy, arthritis, appendicitis, +salpingitis, child-birth, in obstructions of the intestinal +and the genito-urinary tract, in short, in those acute processes +in which the local symptoms are powerful enough to govern +the individual as a whole,--to make him lie down and keep quiet, +refuse food and possibly reject what is already in the stomach,-- +in all these conditions there is rarely a headache, but in the diseases +in which local pain is absent, such as the exanthemata, typhoid fever, +and auto-intoxication, which have no dominating local disturbances +to act as policemen to put the individual to bed and to make him +refuse food that he may be in the most favorable position to combat +the oncoming disease, in such cases in which these masterful and +beneficent local influences are absent we postulate that headache +has been evolved to perform this important service. + +On the hypothesis that it is good for the individual who is acutely +stricken by a disease or who is poisoned by autointoxication to rest +and fast, and that the muscular system obeys the imperial command +of pain, and in view of the fact that the brain is not only in constant +touch with the conditions of every part of the body but that it +is also the controlling organ of the body, one would expect that in +these diseases the major pain whose purpose it is to govern general +muscular action would be located in the head and there we find it. +How curious and yet how intelligible is the fact that, though a +headache may be induced by even a slight auto-intoxication, +an abscess may exist within the brain without causing pain. +When an obliterative endarteritis is threatening a leg with +anemic gangrene, or when one lies too long in the same position on +a hard bed, there is threatening injury from local anemia, and as a +result there is acute pain, but when the obliterative endarteritis +threatens anemia of the brain, or when an embolism or thrombosis has +produced anemia of the brain, there may be no accompanying pain. +The probable explanation of the pain which results in the first instance +and the lack of pain in the second is that in the former muscular action +constitutes a self-protective response, but in the other it does not. +Diseases and injuries of the brain are notoriously difficult +to diagnosticate. This may well be because it has always been so well +protected by the skull that there have been evolved within it few +tell-tale self-protective responses, so that in the presence of injury +and disease within itself the brain remains remarkably silent. +It should occasion no surprise that there are in the brain no receptors, +the mechanical stimulation of which can cause pain, because its bony +covering has always prevented the adaptive implantation within it +of contact pain receptors. Dr. Frazier tells me that in the course +of his operations on the brains of unanesthetized patients +he is able to explore the entire brain freely and without pain. +From my own experience I am able to confirm Dr. Frazier's observation. +In addition, the two-stage operation for the excision of the Gasserian +ganglion provides an observation of extraordinary interest. +If at the first seance the ganglion is exposed, but is not disturbed +except by the iodoform gauze packing, then on the following +day the gauze may be removed, the ganglion picked up, and its +branches and root excised without anesthesia and without pain. +The same statement and explanation may be made regarding the distribution +of pain receptors for physical contact within the parenchyma of the liver, +the gall-bladder, the abdominal viscera, the spleen, the heart, +the lungs, the retroperitoneal tissue, the deep tissue of the back, +the vertebrae, and in certain portions of the spinal cord. +Just what is the distribution of the receptors for heat and for cold +I am unable to state, but this much we do know, that without +anesthesia the intestines may be cauterized freely without the least +pain resulting, and in animals the cauterization of the brain causes +no demonstrable change in the circulatory or respiratory reactions. +It is probable therefore that the distribution of the pain receptors +for physical contact and for heat are limited to those parts of the body +that have been exposed to injurious contacts with environment. + +Of special significance is the pain which is due to cold, +which increases muscular tone and produces shivering. The general +increase in muscular tone produces an interesting postural phenomenon: +the limbs are flexed and the body bent forward, a position which probably +is due to the fact that the flexors are stronger than the extensors. +As muscular action is always accompanied by heat production, +the purpose of the muscular contraction and the shivering +is quite certainly caused by cold to assist in the maintenance +of the normal body temperature. + +We have now discussed many of the causes of pain and in each instance +we have found an associated muscular action which apparently +serves some adaptive purpose (Figs. 24 and 25). If we assume +that pain exists for the purpose of stimulating muscular reactions, +we may well inquire what part of the nervous are is the site of +the sensation of pain--the nerve-endings, the trunk, or the brain? +Does pain result from physical contact with the nerve-endings, with +the physical act of transmitting an impression along the nerve trunk, +or with the process within the brain-cells by which energy is released +to cause a motor act? + +It seems most probable that the site of the pain is in the brain-cells. +If this be so, then what is the physical process by which the +phenomena of pain are produced? The one hypothesis that can be +tested experimentally is that pain is a phenomenon resulting from +the rapid discharge of energy in the brain-cells. If this be true, +then if every pain receptor of the body were equally stimulated +in such a manner that + + +{illust. caption = FIG. 25.--FEAR AND AGONY. "Amid this dread +exuberance of woe ran naked spirits wing'd with horrid fear."-- +Dante's "Inferno," Canto XXIV, lines 89, 90. all the stimuli +reached the brain-cells simultaneously, the cells would find +themselves in equilibrium and no motor act would be performed. +But if all the pain receptors of the body but one were equally stimulated, +and this one stimu-lated harder than the rest, then the latter +would gain possession of the final common path, the sensation +of pain would be felt, and a muscular contraction would result. +It is well known that when a greater pain is thrown into +competition with a lesser one, the lesser is completely submerged. +In this manner the school-boy initiates the novice into the mystery +of the painless plucking of hair. The simultaneous, but severe +application of the boot to the blindfolded victim takes complete +and exclusive possession of the final common path and the hair +is painlessly plucked through the triumph of the boot stimulus over +the hair stimulus in the struggle for the possession of the final +common path. Another argument in favor of this hypothesis that +pain is an accompaniment of the release of energy in the brain- +cells is found in the fact that painless stimuli received through +the special senses may completely submerge the painful stimuli +of physical injury; for although the stimuli to motor action, +which are received through the senses of sight, hearing, and smell, +cause even more powerful motor action than those caused by +physical contact stimuli, yet they are not accompanied by pain. +Examples of this triumph of stimulation of the special senses over +contact stimulation are frequently seen in persons obsessed by anger +or fear, and to a less degree in those obsessed by sexual emotion. +In the fury of battle the soldier may not perceive his wound until +the emotional excitation is wearing away, when the sensation +of warm blood on the skin may first attract his attention. +Religious fanatics are said to feel no pain when they subject themselves +to self-injury. Now, since both psychic and mechanical stimuli cause motor +action by the excitation ofprecisely the same mechanism in the brain, +and since the more rapid release of energy from psychic stimuli +submerges the physical stimuli and prevents pain, it would seem +that pain must be a phenomenon which is associated with the process +of releasing energy by the brain-cells. Were physical injury inflicted +in a quiescent state equal to that inflicted in the emotional state, +great pain and intense muscular action would be experienced. +Now the emotions are as purely motor excitants as is pain. +The dynamic result is the same the principal difference being the greater +suddenness and the absolute specificity of the pain stimuli as compared +with the more complex and less peremptory stimuli of the emotions. +A further evidence that pain is a product of the release of brain-cell +energy is the probability that if one could pierce the skin at +many points on a limb in such a manner that antagonistic points +only were equally and simultaneously stimulated, then an equilibrium +in the governing brain- cells would be established and neither +pain nor motion would follow. An absolute test of this assumption +cannot be made but it is supported by the obtainable evidence. +We will now turn to a new viewpoint, a practical as well as a +fascinating one, which can best be illustrated by two case histories: +A man, seventy-eight years old, whose chief complaint was obstinate +constipation, was admitted to the medical ward of the Lakeside Hospital +several years ago. The abdomen was but slightly distended; +there was no fever, no increased leukocytosis, no muscular rigidity, +and but slight general tenderness. He claimed to have lost in weight +and strength during the several months previous to his admission. +A tentative diagnosis of malignant tumor of the large intestine was made, +but free movements weresecured rather easily, and we abandoned +the idea of an exploratory operation. The patient gradually failed +and died without a definite diagnosis having been made by either +the medical or the surgical service. At autopsy there was found +a wide-spread peritonitis arising from a perforated appendix. +A child, several years old, was taken ill with some indefinite disease. +A number of the ablest medical and surgical consultants of a leading +medical center thoroughly and repeatedly investigated the case. +Although they could make no definite diagnosis they all +agreed that the trouble surely could not be appendicitis +because there was neither muscular rigidity nor tenderness. +The autopsy showed a gangrenous appendix and general peritonitis. +How can these apparently anomalous cases be explained? +These two cases are illustrations of the same principle that underlies +the freedom from pain which results from the use of narcotics +and anesthetics, the same principle that explains the fact that +cholecystitis may occur in the aged without any other local symptoms +than the presence of a mass and perhaps very slight tenderness; +and that accounts in general for the lack of well-expressed disease +phenomena in senility and in infancy. The reason why the aged, +the very young, and the subjects of general paresis show but few +symptoms of disease is that in senility the brain is deteriorated, +while in infancy the brain is so undeveloped that the mechanism +of association is inactive, hence pain and tenderness, +which are among the oldest of the associations, are wanting. +Senility and infancy are by nature normally narcotized. +The senile are passing through the twilight into the night; +while infants are traversing through the dawn into the day. +Hence it is that the diagnosis of injury and disease in the extremes +oflife is beset by especial difficulties, since the entire body +is as silent as are the brain, the pericardium, the mediastinum, +and other symptomless areas. For the same reason, when a patient +who is seriously ill with a painful disease turns upon the physician +a glowing eye and an eager face, and remarks how comfortable he feels, +then the end is near. This is a brilliant and fateful clinical mirage. +When one reflects on the vast amount of evidence as to the origin +and the purpose of pain, he is forced to conclude that pain is +a phenomenon of motor stimulation, and that its principal role is +the protection of the individual against the gross and the microscopic +enemies in his environment. The benefits of pain are especially +manifested in the urgent muscular actions by means of which the body +moves away from physical injury; obstructions of the hollow +viscera are overcome; rest is compelled in the acute infections-- +the infected points are held rigidly quiet, the muscles of the abdomen +are fixed, and harmful peristalsis is arrested in peritonitis; +while there is absolutely no pain in the diseases or injuries +which affect those regions of the body in which in the course +of evolution no pain receptors were placed, or in those diseases +in which muscular inhibition or contraction is of no help. +In a biologic sense pain is closely associated with the emotional stimuli, +for both pain and the emotions incite motor activity for the good +of the individual. The frequent occurrence of post-operative and +post- traumatic pain is accounted for by the fact that the operation +or the injury has lowered the threshold of the brain- cells to trauma; +the brain and not the local sensitive field is the site of the pain. +I have found that, by blockingthe field of operation with +local anesthesia, post-operative pain is diminished; that is, +since the local anesthesia prevents the strong stimuli of the +trauma from reaching the brain, its threshold is not lowered. +There is a close resemblance between the phenomena of pain habit, +of education, of physical training, of love and of hate. In education, +in pain habit, in all emotional relations, a low brain- cell threshold +is established which facilitates the reception of specific stimuli; +all these processes are motor acts, or are symbolic of motor acts, +and we may be trained to perceive misfortune and pain as readily as we +are trained to perceive mathematical formulae or moral precepts. +In each and every case, readiness of perception depends, as it seems to me, +upon a modified state of the brain-cells, their threshold especially, +the final degree of perception possible in any individual being perhaps +based on the type of potential molecules of which the brain is built. +We must believe also that every impression is permanent, as only thus +could an individual animal or a man be fitted by his own experience +for life's battles. LAUGHTER AND CRYING What is laughter? +What is its probable origin, its distribution, and its purpose? +Laughter is an involuntary rhythmic contraction of certain +respiratory muscles, usually accompanied by certain vocal sounds. +It is a motor act of the respiratory apparatus primarily, although if +intense it may involve not only the extraordinary muscles of respiration, +but most of the muscles of the body. There are many degrees +of laughter, from the mere brightening of the eyes, a fleeting smile, +tittering andgiggling, to hysteric and convulsive laughter. +Under certain circumstances, laughter may be so intense and +so long continued that it leads to considerable exhaustion. +The formation of tears is sometimes associated with laughter. +When integrated with laughter, the nervous system can perform +no other function. Crying is closely associated with laughter, +and in children especially laughter and crying are readily interchanged. +We postulate that laughter and weeping serve a useful purpose. +According to Darwin, only man and monkeys laugh (Fig. 26); +other animals exhibit certain types of facial expression accompanying +various emotions, but laughter in the sense in which that word +is commonly used is probably an attribute of the primates only, +although it is probable that many animals find substitutes for laughter. +The proneness of man to laughter is modified by age, sex, training, +mental state, health, and by many other factors. Healthy, happy children +are especially prone to laughter, while disease, strong emotions, +fatigue, and age diminish laughter. Women laugh more than do men. +The healthy, happy maturing young woman perhaps laughs most, especially +when she is slightly embarrassed. What causes laughter? Good news, +high spirits, tickling, hearing and seeing others laugh; droll stories; +flashes of wit; passages of humor; averted injury; threatened breach +of the conventions; and numerous other causes might be added. +It is obvious that laughter may be produced by diverse influences, +many of which are so unlike each other that it would at first sight +seem improbable that a single general principle underlies all. +Before presenting a hypothesis which harmonizes most of the facts, +and which mayoffer an explanation of the origin and purpose of laughter, +let us return for a moment to some previous considerations-- +that man is essentially a motor being; that all his responses to +the physical forces of his environment are motor; {illust. caption += FIG. 26.--LAUGHING CHIMPANZEE. "Mike," the clever chimpanzee +in the London Zoo, evidently enjoys a joke as well as any one else. +(Photo by Underwood and Underwood, N. Y.)} + + +that thoughts and words even are symbolic of motor acts; +that in the emotions of fear, of anger, and of sexual love +the whole body is integrated for acts which are not performed. +These integrations stimulate the brain-cells, the ductless glands, +and other parts, and the energizing secretions, among which are epinephrin, +thyroid and hypophyseal secretions, are thrown into the blood-stream, +while that most available fuel, glycogen, is also mobilized in the blood. +This body-wide preparation for action may be designated kinetic reaction. +The fact that emotion is more injurious to the body than is +muscular action is well known, the difference being probably caused +by the fact that when there is action the above-mentioned products +of stimulation are consumed, while in stimulation without action +they are not consumed and must be eliminated as waste products. +Now these activating substances and the fuel glycogen may be consumed +by any muscular action as well as by the particular muscular action +for which the integration and consequent stimulation were made; +that is, if one were provoked to such anger that he felt impelled +to attack the object of his anger, one of three things might happen: +First, he might perform no physical act but give expression to +the emotion of anger; second, he might engage in a physical struggle +and completely satisfy his anger; third, he might immediately engage +in violent gymnastic exercises and thus consume all the motor-producing +elements mobilized by the anger and thus clarify his body. + +In these premises we find our explanation of the origin and purpose +of laughter and crying, for since they consist almost wholly +of muscular exertion, they serve precisely such clarifying purposes +as would be served by the gymnastic exercises of an angry man. +As it seems to me, the muscular action of laughter clears the system +of the energizing substances which have been mobilized in various +parts of the body for the performance of other actions (Figs. 27 +to 29). If this be true, the first question that presents itself is, +Why is the respiratory system utilized for such a clarifying purpose? +Why do we not laugh with our feet and hands as well? +Were laughter expressed with the hands, the monkey might fall +from the tree and, if by the feet, man might fall to the ground. +He would at least be ataxic. In fact, laughter has the great +advantage of utilizing a group of powerful muscles which can be +readily spared without seriously interfering with the maintenance +of posture. Laughter, however, is only one form of muscular action +which may consume the fuel thrown into the blood by excitation. +That these products of excitation are often consumed by other motor +acts than laughter is frequently seen in public meetings when +the stamping of feet and the clapping of hands in applause gives +relief to the excitation (Fig. 30). Why the noise of laughter? +In order that the products of excitation may be quickly and +completely consumed, the powerful group of expiratory muscles must +have some resistance against which they can exert themselves strongly +and at the same time provide for adequate respiratory exchange. +The intermittent closure of the epiglottis serves this purpose admirably, +just as the horizontal bars afford the resistance against which muscles +may be exercised. The facial muscles are not in use for other purposes, +hence their contractions will consume a little of the fuel. +An audience excited by the words of an impassioned speaker undergoes +a body-wide stimulation for action, all of which may be eliminated +by laughter or by applause (Fig. 31). + +Let us test this hypothesis by some practical examples. +The first is an incident that accidentally occurred in our laboratory +during experiments on fear which were performed as follows: +A keen, snappy fox terrier was completely muzzled by winding a broad strip +of adhesive plaster around his jaw so as to include all but the nostrils. +When this aggressive little terrier and the rabbit found themselves +in close quarters each animal became completely governed by instinct; +the rabbit crouched in fear, while the terrier, with all the ancestral +assurance of seizing his prey, rushed, upon the rabbit, his muzzle +always glancing off and his attack ending in awkward failure. + +This experiment was repeated many times and each time provoked +the serious-minded scientific visitors who witnessed it +to laughter. Why? Because the spectacle of a savage little terrier +rushing upon an innocent rabbit as if to mangle it integrated +the body of the onlooker with a strong desire to exert muscular +action to prevent the cruelty. This integration caused a conversion +of the potential energy in the brain-cells into kinetic energy, +and there resulted a discharge into the blood-stream of activating +internal secretions for the purpose of producing muscular action. +Instantly and unexpectedly the danger passed and the preparation +for muscular action intended for use in the protection of the rabbit +was not needed. This fuel was consumed by the neutral muscular +action of laughter, which thus afforded relief. + +A common example of the same nature is that encountered on the street +when a pedestrian slips on a banana peel and, just as he is +about to tumble, recovers his equilibrium. The onlookers secure +relief from the integration to run to his rescue by laughing. +On the other hand, should the same pedestrian fall and fracture +his skull the motor integration of the onlookers would be consumed +by rendering physical assistance--hence there would be no laughter. +In children almost any unexpected phenomenon, such as a sudden "booing" +from behind a door, is attended by laughter, and in like manner +the kinetic reaction produced by the innumerable threats of danger +which are suddenly averted, a breach of the conventions, a sudden +relief from acute nervous tension; a surprise--indeed, any excitant +to which there is no predetermined method of giving a physical response-- +may be neutralized by the excitation of the mechanism of laughter. + +In the same way the laughter excited by jokes may be explained. +An analysis of a joke shows that it is composed of two parts-- +the first, in which is presented a subject that acts as a stimulus +to action, and the second, in which the story turns suddenly +so that the stimulus to action is unexpectedly withdrawn. +The subject matter of the joke affects each hearer according +to the type of stimuli that commonly excites that individual. +Hence it is that a joke may convulse one person while it bores another, +and so there are jokes of the classes, bankers' jokes, politicians' jokes, +the jokes of professional men, of the plebeian, of the artist, etc. +If the joke fails, the integration products of the excitation may +be used in physical resentment (Fig. 32). + +Another type of laughter is that associated with the ticklish points +of certain parts of the body, the soles of the feet and certain +parts of the trunk and of the abdomen. The excitation of the +ticklish receptors, like pain, compels self-defensive motor acts. +This response is of phylogenetic origin, and may be awakened only +by stimuli which are too light to be painful. In this connection +it is of interest to note that a superficial, insect-like contact +with the skin rarely provokes laughter, and that the tickling +of the nasal, oral, and pulmonary tracts does not produce laughter. +The ticklish points that cause laughter are rather deeply placed, +and a certain type of physical contact is required to constitute +an adequate stimulus. That is, the contact must arouse a phylogenetic +association with a physical struggle or with physical exertion. +In the foot, the adequate stimuli for laughter are such contacts +as resemble or suggest piercing by stones or rough objects.. The +intention of the one who tickles must be known; if his intention +be playful, laughter results, whereas if injury be intended, +then an effort toward escape or defense is excited, but no laughter. +If deep tickling of the ribs is known to be malicious, it will excite +physical resentment and not laughter. Self-tickling rarely causes +laughter for the reason that auto-tickling can cause only a known +degree of stimulation, so that there results no excessive integration +which requires relief by the neutral muscular activity of laughter. +In fact, one never sees purposeful acts and laughter associated. +According to its severity, an isolated stimulus causes either +an action or laughter. The ticklish points in our bodies were +probably developed as a means of defense against serious attacks +and of escape from injurious contacts. + +Anger, fear, and grief are also strong excitants and, therefore, +are stimuli to motor activity. It is obvious that whatever the excitant +the physico-chemical action of the brain and the ductless glands +cannot be reversed--the effect of the stimulus cannot be recalled, +therefore either a purposeful muscular act or a neutralizing act +must be performed or else the liberated energy must smoulder +in the various parts of the body. + +It is on this hypothesis that the origin and the purpose of laughter +and crying may be understood. Even a superficial analysis of the +phenomena of both laughter and crying show them to be without any +external motor purpose; the respiratory mechanism is intermittently +stimulated and inhibited; and the shoulder and arm muscles, indeed, +many muscles of the trunk and the extremities are, as far as any +external design is concerned, purposelessly contracted and released +until the kinetic energy mobilized by excitation is utilized. +During this time the facial expression gives the index to +the mental state. + +Crying, like laughter, is always preceded by a stimulation +to some motor action which may or may not be performed +(Figs. 33 and 34). If a mother is anxiously watching the course +of a serious illness of her child and if, in caring for it, she is +stimulated to the utmost to perform motor acts, she will continue +in a state of motor tenseness until the child recovers or dies. +If relief is sudden, as in the crisis of pneumonia, and the mother +is not exhausted, she will easily laugh if tired, she may cry. +If death occurs, the stimulus to motor acts is suddenly +withdrawn and she then cries aloud, and performs many motor +acts as a result of the intense stimulation to motor activity +which is no longer needed in the physical care of her child. +With this clue we can find the explanation of many phenomena. We can +understand why laughter and crying are so frequently interchangeable; +why they often blend and why either gives a sense of relief; +we can understand why either laughter or crying can come only +when the issue that causes the integration is determined; we can +understand the extraordinary tendency to laughter that discloses +the unspoken sentiments of love; we can understand the tears +of the woman when she receives a proposal of marriage from the man +she loves; we can understand why any averted circumstance, +such as a threatened breach of the conventions, which would have led +to embarrassment or humiliation, leads to a tendency to laughter; +and why the recital of heroic deeds by association leads to tears, +On the other hand, under the domination of acute diseases, +of acute fear, or of great exhaustion, there is usually neither +laughter nor crying because the nervous system is under the control +of a dominating influence as a result of which the body is so +exhausted that the excess of energy which alone can produce laughing +or crying is lacking. + +A remarkable study of the modification of laughter and crying by disease +is found in that most interesting of diseases--exophthalmic goiter. +In this disease there is a low threshold to all stimuli. +That the very motor mechanism of which we have been speaking +is involved, is shown by an enormous increase in its activity. +There is also an increase in the size of certain at least of the +activating glands--the thyroid and the adrenals are enlarged and overactive +and the glycogen-producing function of the liver is stimulated. +The most striking phenomenon of this disease, however, is the remarkable +lowering of the brain thresholds to stimuli. In other words, +in Graves' disease the nervous system and the activating glands-- +the entire motor mechanism--are in an exalted state of activity. + +If this be true, then these patients should exhibit behavior +precisely contrary to that of those suffering from acute infection, +that is, they should be constantly clearing their systems of +these superabundant energizing materials by crying or laughing, +and this is precisely what happens--the flood-gates of tears are open +much of the time in Graves' disease--a disease of the emotions. + +We have already interpreted pain as a phenomenon of motor activity. +When pain does not lead to muscular activity it therefore frequently +leads to crying or to moaning, just as tickling, which is equally +an incentive to motor activity, results in laughter if it does +not find full expression in action. + +From the foregoing we infer that pain, the intense motor response +to tickling, and emotional excitation are all primitive biologic +reactions for the good of the individual, and that all have +their origin in the operation of the great laws of evolution. +If to this inference we add the physiologic dictum that the nervous +system always acts as a whole, and that it can respond to but one +stimulus at a time, we can easily understand that while diverse +causes may integrate the nervous system for a specific action, +if the cause be suddenly removed, then the result of the +integration of the nervous system may be, not a specific action, +but an undesigned muscular action, such as crying or laughter. +Hence it is that laughter and crying may be evoked by diverse +exciting causes. The intensity of the laughter or of the crying +depends upon the intensity of the stimulus and the dynamic state +of the individual. + +The linking together of these apparently widely separated phenomena +by the simple law of the discharge of energy by association perhaps +explains the association of an abnormal tendency to tears with an +abnormally low threshold for pain (Fig. 36). In the neurasthenic, +tears and pain are produced with abnormal facility. Hence it is that, +if a patient about to undergo a surgical operation is in a state of fear +and dread before the operation, the threshold to all stimuli is lowered, +and this lowered threshold will continue throughout the operation, +even under inhalation anesthesia, because the stimulus produced by +cutting sensitive tissue is transmitted to the brain just as readily +as if the patient were not anesthetized. In like manner, the brain +may be sensitized by the administration of large doses of thyroid +extract prior to operation, the threshold to injury in such a case +continuing to be low to traumatic stimuli even under anesthesia. +Under the sensitizing influences of thyroid extract or of Graves' +disease the effect of an injury, of an operation, or of emotional +excitation is heightened. The extent to which the threshold to pain +or to any other excitant is affected by Graves' disease is illustrated +by the almost fatal reaction which I once saw result from the mere +pricking with a hypodermic needle of a patient with this disease. +As the result of a visit from a friend, the pulse-rate of a victim of this +disease may increase twenty beats and his temperature rise markedly. +I have seen the mere suggestion of an operation produce collapse. +As the brain is thus remarkably sensitized in Graves' disease, we find +that in these patients laughter, crying, emotional disturbances, +and surgical shock are produced with remarkable facility. + +I hope that even this admittedly crude and imperfect consideration +of this subject will suggest the possibility of establishing +a practical viewpoint as to the origin and purpose of pain, +of tickling, and of such expressions of emotion as laughter and crying, +and that it may help us to understand their significance in health +and in disease. + + + +THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND +BRAIN FUNCTIONS--EXPERIMENTAL AND CLINICAL[*] + +[*] Address before The American Philosophical Society, April 18, 1913. + + +The brain in all animals (including man) is but the clearing-house +for reactions to environment, for animals are essentially motor +or neuromotor mechanisms, composed of many parts, it is true, +but integrated by the nervous system. Throughout the phylogenetic history +of the race the stimuli of environment have driven this mechanism, +whose seat of power--the battery--is the brain. + +Since all normal life depends upon the response of the brain +to the daily stimuli, we should expect in health, as well +as in disease, to find modifications of the functions and the +physical state of the component parts of this central battery-- +the brain-cells. Although we must believe, then, that every +reaction to stimuli, however slight, produces a corresponding +change in the brain-cells, yet there are certain normal, that is, +non-diseased, conditions which produce especially striking changes. +The cell changes due to the emotions, for example, are so similar, +and in extreme conditions approach so closely to the changes produced +by disease, that it is impossible to say where the normal ceases +and the abnormal begins. + +In view of the similarity of brain-cell changes it is not strange +that in the clinic as well as in daily life, we are confronted +constantly by outward manifestations which are so nearly +identical that the true underlying cause of the condition in +any individual case is too often overlooked or misunderstood. +In our laboratory experiments and in our clinical observations +we have found that exhaustion produced by intense emotion, +prolonged physical exertion, insomnia, intense fear, certain toxemias, +hemorrhage, and the condition commonly denominated surgical shock, +produce similar outward manifestations and identical brain-cell changes. + +It is, therefore, the purpose of this paper to present the definite +results of laboratory researches which show certain relations +between alterations in brain functions and physical changes +in the brain-cells. + +Fear.--Our experiments have shown that the brain-cell changes due +to fear may be divided into two stages: First, that of hyperchromatism-- +stimulation; second, that of hypochromatism--exhaustion (Figs. 5 and +13). Hyperchromatism was shown only in the presence of the activating +stimuli or within a very short time after they had been received. +This state gradually changed until the period of maximum exhaustion +was reached--about six hours later. Then a process of reconstruction +began and continued until the normal state was again reached. + +Fatigue.--Fatigue from overexertion produced in the brain-cells +like changes to those produced by fear, these changes being +proportional to the amount of exertion (Fig. 4). In the extreme +stage of exhaustion from this cause we found that the total +quantity of Nissl substance was enormously reduced. +When the exertion was too greatly prolonged, it took weeks or +months for the cells to be restored to their normal condition. +We have proved, therefore, that in exhaustion resulting from emotion +or from physical work a certain number of the brain-cells are +permanently lost. This is the probable explanation of the fact +that an athlete or a race-horse trained to the point of highest +efficiency can reach his maximum record but once in his life. +Under certain conditions, however, it is possible that, though some +chromatin is forever lost, the remainder may be so remarkably developed +that for a time at least it will compensate for that which is gone. + +Hemorrhage.--The loss of blood from any cause, if sufficient to reduce +the blood-pressure, will occasion a change in the brain-cells, provided +that the period of hypotension lasts for more than five minutes. +This time limit is a safeguard against permanent injury +from the temporary hypotension which causes one to faint. +If the hemorrhage be long continued and the blood-pressure be low, +there will be a permanent loss of some of the brain-cells. This +explains why an individual who has suffered from a prolonged +hemorrhage will never again be restored to his original powers. + +Drugs.--According to their effect upon the brain-cells, drugs +may be divided into three classes: First, those that stimulate +the brain-cells to increased activity, as strychnin (Fig. 37); +second, those that chemically destroy the brain-cells, as alcohol +and iodoform (Figs. 38 and 39); third, those that suspend the functions +of the cells without damaging them, as nitrous oxid, ether, morphin. +Our experiments have shown that the brain-cell changes induced +by drugs of the first class are precisely the same as the cycle +of changes produced by the emotions and by physical activity. +We have found that strychnin, according to the dosage, causes convulsions +ending in exhaustion and death; excitation followed by lassitude; +stimulation without notable after-results; or + + +{illust. caption = A, Section of Cerebellum of Normal Dog. C, Section of +Cerebellum of Dog after Repeated Doses of Strychnin. FIG. 37.-- +BRAIN-CELLS SHOWING STAGE OF HYPERCHROMATISM FOLLOWED BY CHROMATOLYSIS +RESULTING FROM THE CONTINUATION OF THE STIMULUS. (Camera lucida +drawings.)increased mental tone; while the brain-cells accurately +display these physiologic alterations in proportional hyperchromatism +in the active stages, and proportional chromatolysis in the stages +of reaction. The biologic and therapeutic application of this fact +is as obvious as it is important. + +In our experiments, alcohol in large and repeated dosage caused +marked morphologic changes in the brain-cells which went as far +even as the destruction of some of the cells (Fig. 39). Ether, +on the other hand, even after five hours of administration, +produced no observable destructive changes in the brain-cells. + +The effect of iodoform was peculiarly interesting, as it was the only +drug that produced a rise of temperature. Its observed effect upon +the brain-cells was that of wide-spread destruction. + +Infections.--In every observation regarding the effect of pyogenic +infections on dogs and on man we found that they caused definite +and demonstrable lesions in certain cells of the nervous system, +the most marked changes being in the cortex and the cerebellum +(Fig. 40). For example, in fatal infections resulting from +bowel obstruction, in peritonitis, and in osteomyelitis, the real +lesion is in the brain-cells. We may, therefore, reasonably conclude +that the lassitude, the diminished mental power, the excitability, +irritability, restlessness, delirium, and unconsciousness which may +be associated with acute infections, are due to physical changes +in the brain-cells. + +Graves' Disease.--In Graves' disease the brain-cells show marked +changes which are apparently the same as those produced by overwork, +by the emotions, and by strychnin. In the postmortem examination +of one advanced case it was found that a large number of brain-cells +were disintegrated beyond the power of recuperation, even had +the patient lived. This is undoubtedly the reason why a severe case +of exophthalmic goiter sustains a permanent loss of brain power. + +Insomnia.--The brains of rabbits which had been kept awake for one +hundred hours showed precisely the same changes as those shown +in physical fatigue, strychnin poisoning, and exhaustion from +emotional stimulation. Eight hours of continuous sleep restored +all the cells except those that had been completely exhausted. +This will explain the permanent ill effect of long-continued insomnia; +that is, long-continued insomnia permanently destroys a part +of the brain-cells just as do too great physical exertion, +certain drugs, emotional strain, exophthalmic goiter, and hemorrhage. +We found, however, that if, instead of natural sleep, the rabbits +were placed for the same number of hours under nitrous oxid anesthesia, +not only did the brain-cells recover from the physical deterioration, +but that 90 per cent. of them became hyperchromatic. +This gives us a possible clue to the actual chemical effect of sleep. +For since nitrous oxid owes its anesthetic effect to its influence +upon oxidation, we may infer that sleep also retards the oxidation +of the cell contents. If this be true, then it is probable +that inhalation anesthetics exert their peculiar influence upon +that portion of the brain through which sleep itself is produced. +If nitrous oxid anesthesia and sleep are chemically identical, then we +have a further clue to one of the primary mechanisms of life itself; +and as a practical corollary one might be able to produce artificial +sleep which would closely resemble normal sleep, but which would +have this advantage, that by using an anesthetic which interferes with +oxidation the brain-cells might be reconstructed after physical fatigue, +after emotional strain, or after the depression of disease. + +In the case of the rabbit in which nitrous oxid was substituted +for sleep, the appearance of the brain-cells resembled that in +but one other group experimentally examined--the brain-cells +of hibernating woodchucks. + +Insanity.--Our researches have shown that in the course of a fatal +disease and in fatal exhaustion, however produced, death does not +ensue until there is marked disorganization of the brain tissue. +In the progress of disease or exhaustion one may see in different +patients every outward manifestation of mental deterioration, +manifestations which, in a person who does not show any other sign of +physical disease, mark him as insane. Take, for example, the progressive +mental state of a brilliant scholar suffering from typhoid fever. +On the first day of the gradual onset of the disease he would +notice that his mental power was below its maximum efficiency; +on the second he would notice a further deterioration, and so +the mental effect of his disease would progress until he would +find it impossible to express a thought or to make a deduction. +No one can be philanthropic with jaundice; no one suffering +from Graves' disease can be generous; no mental process is possible +in the course of the acute infectious diseases. Just prior to death +from any cause every one is in a mental state which, if it could +be continued, would cause that individual to be judged insane. +If the delirium that occurs in the course of certain diseases +should be continued, the patient would be judged insane. +In severe cases of Graves' disease the patient is insane. +Individuals under overwhelming emotion may be temporarily insane. +Every clinician has seen great numbers of cases in which insanity +is a phase of a disease, of an injury, or of an emotion. +The stage of excitation in anesthesia is insanity. +The only difference between what is conventionally called insanity +and the fleeting insanity of the sick and the injured is that of time. +We may conclude, therefore, what must be the brain-picture of the person +who is permanently insane. This _a priori_ reasoning is all that +is possible, since the study of the brain in the insane has thus far +been confined to the brains of those who have died of some disease. +And it is impossible to say which changes have been produced by the +fatal disease, and which by the condition which produced the insanity. +The only logical way by which to investigate the physical basis +of insanity would be to make use of the very rare opportunities +of studying the brains of insane persons who have died in accidents. + +Our experiments have proved conclusively that whether we call a person +fatigued or diseased, the brain-cells undergo physical deterioration, +accompanied by loss of mental power (Figs. 40 to 43). Even to the minutest +detail we can show a direct relationship between the physical state +of the brain-cells and the mental power of the individual, that is, +the physical power of a person goes _pari passu_ with his mental power. +Indeed, it is impossible to conceive how any mental action, +however subtle, can occur without a corresponding change in the +brain-cells. It is possible now to measure only the evidences of +the effects on the brain-cells of gross and violent mental activity. +At some future time it will doubtless be possible so to refine +the technic of brain-cell examinations that more subtle changes +may be measured. Nevertheless, with the means at our disposal +we have shown already that in all the conditions which we +have studied the cells of the cortex show the greatest changes, +and that loss of the higher mental functions invariably accompanies +the cell deterioration. + + + + +A MECHANISTIC VIEW OF PSYCHOLOGY[*] + + +[*] Address delivered before Sigma Xi, Case School +of Science, Cleveland, Ohio, May 27, 1913, and published +in _Science_, August 29, 1913. + + +Traditional religion, traditional medicine, and traditional psychology +have insisted upon the existence in man of a triune nature. +Three "ologies" have been developed for the study of each nature +as a separate entity--body, soul, and spirit--physiology, psychology, +theology; physician, psychologist, priest. To the great minds +of each class, from the days of Aristotle and Hippocrates on, +there have come glimmerings of the truth that the phenomena +studied under these divisions were interrelated. Always, however, +the conflict between votaries of these sciences has been sharp, +and the boundary lines between them have been constantly changing. +Since the great discoveries of Darwin, the zoologist, biologist, +and physiologist have joined hands, but still the soul-body-spirit +chaos has remained. The physician has endeavored to fight the gross +maladies which have been the result of disordered conduct; +the psychologist has reasoned and experimented to find the laws +governing conduct; and the priest has endeavored by appeals to an +unknown god to reform conduct. + +The great impulse to a deeper and keener study of man's relation, +not only to man, but to the whole animal creation, which was given +by Darwin, has opened the way to the study of man on a different basis. +Psychologists, physicians, and priests are now joining hands as never +before in the great world-wide movement for the betterment of man. +The new science of sociology is combining the functions of all three, +for priest, physician, and psychologist have come to see that man +is in large measure the product of his environment. + +My thesis to-night, however, will go beyond this common agreement, +for I shall maintain, not that man is in _*large measure_ the product +of his environment, but that environment has been the actual CREATOR +of man; that the old division between body, soul, and spirit +is non-existent; that man is a unified mechanism responding in every +part to the adequate stimuli given it from without by the environment +of the present and from within by the environment of the past, +the record of which is stored in part in cells throughout +the mechanism, but especially in its central battery--the brain. +I postulate further that the human body mechanism is equipped, first, +for such conflict with environment as will tend to the preservation +of the individual; and, second, for the propagation of the species, +both of these functions when most efficiently carried out tending +to the upbuilding and perfection of the race. + +Through the long ages of evolution the human mechanism has been +slowly developed by the constant changes and growth of its parts +which have resulted from its continual adaptation to its environment. +In some animals the protection from too rough contact with +surroundings was secured by the development of an outside armor; +in others noxious secretions served the purposes of defense, +but such devices as these were not suitable for the higher animals +nor for the diverse and important functions of the human race. +The safety of the higher animals and of man had to be preserved +by some mechanism by means of which they could become adapted +to a much wider and more complex environment, the dominance over +which alone gives them their right to be called "superior beings." +The mechanism by the progressive development of which living +beings have been able to react more and more effectually to their +environment is the central nervous system, which is seen in one +of its simplest forms in motor plants, such as the sensitive +plant and the Venus fly-trap, and in its highest development only +in the sanest, healthiest, happiest, and most useful men. + +The essential function of the nervous system was primarily to secure +some form of motor activity, first as a means of securing food, +and later as a means of escaping from enemies and to promote procreation. +Activities for the preservation of the individual and of the species +were and are the only purposes for which the body energy is expended. +The central nervous system hag accordingly been developed for the purpose +of securing such motor activities as will best adapt the individuals +of a species for their self-preservative conflict with environment. + +It is easy to appreciate that the simplest expressions of nerve response-- +the reflexes--are motor in character, but it is difficult to understand +how such intangible reactions as love, hate, poetic fancy, or moral +inhibition can be also the result of the adaptation to environment +of a distinctively motor mechanism. We expect, however, to prove +that so-called "psychic" states as well as the reflexes are products +of adaptation; that they occur automatically in response to adequate +stimuli in the environment; that, like the reflexes, they are +expressions of motor activity, which, although intangible and unseen, +in turn incite to activity the units of the motor mechanism of the body; +and finally, that any "psychic" condition results in a definite depletion +of the potential energy in the brain-cells which is proportionate +to the muscular exertion of which it is the representative. + +That this nerve mechanism may effectively carry out its +twofold function, first, of self-adaptation to meet adequately +the increasingly complicated stimuli of environment; and second, +of adapting the motor mechanism to respond adequately to its demands, +there have been implanted in the body numerous nerve ceptors-- +some for the transmission of stimuli harmful to the mechanism-- +nociceptors some of a beneficial character--beneceptors; and still +others more highly specialized, which partake of the nature of both +bene- and nociceptors--the distance ceptors, or special senses. + +A convincing proof that environment has been the creator +of man is seen in the absolute adaptation of the nociceptors +as manifested in their specific response to adequate stimuli, +and in their presence in only those parts of the body which throughout +the history of the race have been most exposed to harmful contacts. +We find they are most numerous in the face, the neck, the abdomen, +the hands, and the feet; while in the back they are few in number, +and within the bony cavities they are lacking. + +Instances of the specific responses made by the nociceptors might be +multiplied indefinitely. Sneezing, for example, is a specific response +made by the motor mechanism to stimulation of nociceptors in the nose, +while stimulation of the larynx does not produce a sneeze, but a cough; +stimulation of the nociceptors of the stomach does not produce cough, +but vomiting; stimulation of the nociceptors of the intestine +does not produce vomiting, but increased peristaltic action. +There are no nociceptors misplaced; none wasted; none that do not +make an adequate response to adequate stimulation. + +Another most significant proof that the environment of the past +has been the creator of the man of to-day is seen in the fact +that man has added to his environment certain factors to which +adaptation has not as yet been made. For example, heat is +a stimulus which has existed since the days of prehistoric man, +while the _x_-ray is a discovery of to-day; to heat, the nociceptors +produce an adequate response; to the _x_-ray there is no response. +There was no weapon in the prehistoric ages which could move at +the speed of a bullet from the modern rifle, therefore, while slow +penetration of the tissues produces great pain and muscular response, +there is no response to the swiftly moving bullet. + +The response to contact stimuli then depends always on the presence +of nociceptors in the affected part of the body and to the type +of the contact. Powerful response is made to crushing injury by +environmental forces; to such injuring contacts as resemble the impacts +of fighting; to such tearing injuries as resemble those made by teeth +and claws (Fig. 9). On the other hand, the sharp division of tissue +by cutting produces no adaptive response; indeed, one might imagine +that the body could be cut to pieces by a superlatively sharp knife +applied at tremendous speed without material adaptive response. + +These examples indicate how the history of the phylogenetic experiences +of the human race may be learned by a study of the position +and the action of the nociceptors, just as truly as the study +of the arrangement and variations in the strata of the earth's +crust discloses to us geologic history. + +These adaptive responses to stimuli are the result of the action +of the brain-cells, which are thus continually played upon by +the stimuli of environment. The energy stored in the brain-cells +in turn activates the various organs and parts of the body. +If the environmental impacts are repeated with such frequency that +the brain-cells have no time for restoration between them, the energy +of the cells becomes exhausted and a condition of shock results. +Every action of the body may thus be analyzed into a stimulation +of ceptors, a consequent discharge of brain-cell energy, +and a final adaptive activation of the appropriate part. +Walking, running, and their modifications constitute an adaptation +of wonderful perfection, for, as Sherrington has shown, +the adaptation of locomotion consists of a series of reflexes-- +ceptors in the joints, in the limb, and in the foot being stimulated +by variations in pressure. + +As we have shown, the bene- and nociceptors orientate man to all +forms of physical contact--the former GUIDE HIM TO the acquisition +of food and to sexual contact; the latter DIRECT HIM FROM contacts +of a harmful nature. The distance ceptors, on the other hand, +adapt man to his distant environment by means of communication +through unseen forces--ethereal vibrations produce sight; air waves +produce sound; microscopic particles of matter produce smell. +The advantage of the distance ceptors is that they allow time +for orientation, and because of this great advantage the majority +of man's actions are responses to their adequate stimuli. +As Sherrington has stated, the greater part of the brain has been +developed by means of stimuli received through the special senses, +especially through the light ceptors, the optic nerves. + +We have just stated that by means of the distance ceptors animals +and man orientate themselves to their distant environment. +As a result of the stimulation of the special senses chase and escape +are effected, fight is conducted, food is secured, and mates are found. +It is obvious, therefore, that the distance ceptors are the primary +cause of continuous and exhausting expenditures of energy. +On the other hand, stimuli applied to contact ceptors lead to short, +quick discharges of nervous energy. The child puts his hand +in the fire and there is an immediate and complete response +to the injuring contact; he sees a pot of jam on the pantry shelf +and a long train of continued activities are set in motion, +leading to the acquisition of the desired object. + +The contact ceptors do not at all promote the expenditure of energy +in the chase or in fight, in the search for food or for mates. +Since the distance ceptors control these activities, one would expect to +find that they control also those organs whose function is the production +of energizing internal secretions. Over these organs--the thyroid, +the adrenals, the hypophysis--the contact ceptors have no control. +Prolonged laboratory experimentation seems to prove this postulate. +According to our observations, no amount of physical trauma inflicted upon +animals will cause hyperthyroidism or increased adrenalin in the blood, +while fear and rage do produce hyperthyroidism and increased adrenalin +(Fig. 44) (Cannon). This is a statement of far-reaching importance +and is the key to an explanation of many chronic diseases-- +diseases which are associated with the intense stimulation of +the distance ceptors in human relations. + +Stimuli of the contact ceptors differ from stimuli of the distance +ceptors in still another important particular. The adequacy of stimuli +of the contact ceptors depends upon their number and intensity, +while the adequacy of the stimuli of the distance ceptors depends +upon the EXPERIENCE of the species and of the individual. +That is, according to phylogeny and ontogeny this or that sound, +this or that smell, this or that sight, through association +recapitulates the experience of the species and of the individual-- +awakens the phylogenetic and ontogenetic memory. In other words, sights, +sounds, and odors are symbols which awaken phylogenetic association. +If a species has become adapted to make a specific response to a +certain object, then that response will occur automatically in an +individual of that species when he hears, sees, or smells that object. +Suppose, for example, that the shadow of a hawk were to fall +simultaneously on the eyes of a bird, a rabbit, a cow, and a boy. +That shadow would at once activate the rabbit and the bird to an +endeavor to escape, each in a specific manner according to its +phylogenetic adaptation; the cow would be indifferent and neutral; +while the boy, according to his personal experience or ontogeny, +might remain neutral, might watch the flight of the hawk with interest +or might try to shoot it. + +Each phylogenetic and each ontogenetic experience by an indirect +method develops its own mechanism of adaptation in the brain; +and the brain threshold is raised or lowered to stimuli by +the strength and frequency of repetition of the experience. +Thus through the innumerable symbols supplied by environment the distance +ceptors drive this or that animal according to the type of brain +pattern and the particular state of threshold which has been developed +in that animal by its phylogenetic and ontogenetic experiences. +The brain pattern depends upon his phylogeny, the state of threshold +upon his ontogeny. Each BRAIN PATTERN is created by some particular +element in the environment to which an adaptation has been made +for the good of the species. The _*state of threshold_ depends +upon the effect made upon the individual by his personal contacts +with that particular element in his environment. The presence +of that element produces in the individual an associative recall +of the adaptation of his species--that is, the brain pattern developed +by his phylogeny becomes energized to make a specific response. +The intensity of the response depends upon the state of threshold-- +that is, upon the associative recall of the individual's +own experience--his ontogeny. + +If the full history of the species and of the individual +could be known in every detail, then every detail of that +individual's conduct in health and disease could be predicted. +Reaction to environment is the basis of conduct, of moral standards, +of manners and conventions, of work and play, of love and hate, +of protection and murder, of governing and being governed, in fact, +of all the reactions between human beings--of the entire web of life. +To quote Sherrington once more: "Environment drives the brain, +the brain drives the various organs of the body." + +By what means are these adaptations made? What is the mechanism through +which adequate responses are made to the stimuli received by the ceptors? +We postulate that in the brain there are innumerable patterns +each the mechanism for the performance of a single kind of action, +and that the brain-cells supply the energy--electric or otherwise-- +by which the act is performed; that the energy stored in the brain-cells +is in some unknown manner released by the force which activates +the brain pattern; and that through an unknown property of these brain +patterns each stimulus causes such a change that the next stimulus +of the same kind passes with greater facility. + +Each separate motor action presumably has its own mechanism-- +brain pattern--which is activated by but one ceptor and by +that ceptor only when physical force of a certain intensity +and rate of motion is applied. This is true both of the visible +contacts affecting the nociceptors and of the invisible contacts +by those intangible forces which affect the distance ceptors. +For example, each variation in speed of the light-producing +waves of ether causes a specific reaction in the brain. +For one speed of ether waves the reaction is the perception +of the color blue; for another, yellow; for another, violet. +Changes in the speed of air waves meet with specific response +in the brain patterns tuned to receive impressions through the +aural nerves, and so we distinguish differences in sound pitch. +If we can realize the infinite delicacy of the mechanisms adapted +to these infinitesimal variations in the speed and intensity of +invisible and intangible stimuli, it will not be difficult to conceive +the variations of brain patterns which render possible the specific +responses to the coarser contacts of visible environment. + +Each brain pattern is adapted for but one type of motion, +and so the specific stimuli of the innumerable ceptors play +each upon its own brain pattern only. In addition, each brain +pattern can react to stimuli applied only within certain limits. +Too bright a light blinds; too loud a sound deafens. No mechanism +is adapted for waves of light above or below a certain rate of speed, +although this range varies in different individuals and in different +species according to the training of the individual and the need +of the species. + +We have already referred to the fact that there is no receptive +mechanism adapted to the stimuli from the _x_-ray, from the +high-speed bullet, from electricity. So, too, there are innumerable +forces in nature which can excite in man no adaptive response, +since there exist in man no brain patterns tuned to their waves, +as in the case of certain ethereal and radioactive forces. + +On this mechanistic basis the emotions may be explained as activations +of the entire motor mechanism for fighting, for escaping, for copulating. +The sight of an enemy stimulates in the brain those patterns formed +by the previous experiences of the individual with that enemy, and also +the experiences of the race whenever an enemy had to be met and overcome. +Each of these many brain patterns in turn activates that part of +the body through which lies the path of its own adaptive response-- +those parts including the special energizing or activating organs. +Laboratory experiments show that in an animal driven strongly +by emotion the following changes may be seen: (1) A mobilization +of the energy-giving compound in the brain-cells, evidenced by a +primary increase of the Nissl substance and a later disappearance +of this substance and the deterioration of the cells (Figs. 5 and 13); +(2) increased output of adrenalin (Cannon), of thyroid secretion, +of glycogen, and an increase of the power of oxidation in the muscles; +(3) accelerated circulation and respiration with increased +body temperature; (4) altered metabolism. All these are adaptations +to increase the motor efficiency of the mechanism. In addition, +we find an inhibition of the functions of every organ and tissue that +consumes energy, but does not contribute directly to motor efficiency. +The mouth becomes dry; the gastric and pancreatic secretions are +lessened or are completely inhibited; peristaltic action stops. +The obvious purpose of all these activations and inhibitions is +to mass every atom of energy upon the muscles that are conducting +the defense or attack. + +So strong is the influence of phylogenetic experience that though +an enemy to-day may not be met by actual physical attack, +yet the decks are cleared for action, as it were, and the weapons +made ready, the body as a result being shaken and exhausted. +The type of emotion is plainly declared by the activation +of the muscles which would be used if the appropriate physical +action were consummated. In anger the teeth are set, the fists +are clenched, the posture is rigid; in fear the muscles collapse, +the joints tremble, and the running mechanism is activated +for flight; in sexual excitement the mimicry is as obvious. +The emotions, then, are the preparations for phylogenetic activities. +If the activities are consummated, the fuel--glycogen--and the activating +secretions from the thyroid, the adrenals, the hypophysis are consumed. +In the activation without action, these products must be eliminated +as waste products and so a heavy strain is put upon the organs +of elimination. It is obvious that the body under emotion might be +clarified by active muscular exercise, but the subject of the emotion +is so strongly integrated thereby that it is difficult for him +to engage in diverting, clarifying exertion. The person in anger +does not want to be saved from the ill effects of his own emotion; +he wants only to fight; the person in fear wants only to escape; +the person under sexual excitement wants only possession. + +All the lesser emotions--worry, jealousy, envy, grief, disappointment, +expectation--all these influence the body in this manner, the consequences +depending upon the intensity of the emotion and its protraction. +Chronic emotional stimulation, therefore, may fatigue or exhaust +the brain and may cause cardiovascular disease, indigestion, Graves' +disease, diabetes, and insanity even. + +The effect of the emotions upon the body mechanism may be compared +to that produced upon the mechanism of an automobile if its engines +are kept running at full speed while the machine is stationary. +The whole machine will be shaken and weakened, the batteries and weakest +parts being the first to become impaired and destroyed, the length +of usefulness of the automobile being correspondingly limited. + +We have shown that the effects upon the body mechanism of the action +of the various ceptors is in relation to the response made by the brain +to the stimuli received. What is this power of response on the part +of the brain but CONSCIOUSNESS? If this is so, then consciousness +itself is a reaction to environment, and its intensity must vary +with the state of the brain and with the environmental stimuli. +If the brain-cells are in the state of highest efficiency, if their +energy has not been drawn upon, then consciousness is at its height; +if the brain is fatigued, that is, if the energy stored in the cells +has been exhausted to any degree, then the intensity of consciousness +is diminished. So degrees of consciousness vary from the height +maintained by cells in full vigor through the stages of fatigue +to sleep, to the deeper unconsciousness secured by the administration +of inhalation anesthetics, to that complete unconsciousness +of the environment which is secured by blocking the advent to +the brain of all impressions from both distance and contact ceptors, +by the use of both local and inhalation anesthetics--the state +of anoci-association (Fig. 14). + +Animals and man may be so exhausted as to be only semi-conscious. +While a brain perfectly refreshed by a long sleep cannot immediately +sleep again, the exhausted brain and the refreshed brain when subjected +to equal stimuli will rise to unequal heights of consciousness. +The nature of the physical basis of consciousness has been +sought in experiments on rabbits which were kept awake from +one hundred to one hundred and nine hours. At the end of this +time they were in a state of extreme exhaustion and seemed +semi-conscious. If the wakefulness had been further prolonged, +this state of semi-consciousness would have steadily changed +until it culminated in the permanent unconsciousness of death. +An examination of the brain-cells of these animals showed physical +changes identical with those produced by exhaustion from other causes, +such as prolonged physical exertion or emotional strain (Figs. 45 +and 46). After one hundred hours of wakefulness the rabbits were +allowed a long period of sleep. All the brain-cells were restored +except those that had been in a state of complete exhaustion. +A single seance of sleep served to restore some of the cells, +but those which had undergone extreme changes required prolonged rest. +These experiments give us a definite physical basis for explaining +the cost to the body mechanism of maintaining the conscious state. +We have stated that the brain-cell changes produced by prolonged +consciousness are identical with those produced by physical exertion +and by emotional strain. Rest, then, and especially sleep, +is needed to restore the physical state of the brain-cells which +have been impaired, and as the brain-cells constitute the central +battery of the body mechanism, their restoration is essential +for the maintenance of normal vitality. + +In ordinary parlance, by consciousness we mean the activity +of that part of the brain in which associative memory resides, +but while associative memory is suspended the activities of the brain +as a whole are by no means suspended; the respiratory and circulatory +centers are active, as are those centers which maintain muscular tone. +This is shown by the muscular response to external stimuli made +by the normal person in sleep; by the occasional activation of motor +patterns which may break through into consciousness causing dreams; +and finally by the responses of the motor mechanism made to the injuring +stimuli of an operation on a patient under inhalation anesthesia only. + +Direct proof of the mechanistic action of many of life's phenomena +is lacking, but the proof is definite and final of the part +that the brain-cells play in maintaining consciousness; +of the fact that the degree of consciousness and mental +efficiency depends upon the physical state of the brain-cells; +and finally that efficiency may be restored by sleep, +provided that exhaustion of the cells has not progressed too far. +In this greatest phenomenon of life, then, the mechanistic theory +is in harmony with the facts. + +Perhaps no more convincing proof of our thesis that the body is +a mechanism developed and adapted to its purposes by environment +can be secured than by a study of that most constant manifestation +of consciousness--pain. + +Like the other phenomena of life, pain was undoubtedly evolved +for a particular purpose--surely for the good of the individual. +Like fear and worry, it frequently is injurious. What then may +be its purpose? + +We postulate that pain is a result of contact ceptor stimulation +for the purpose of securing protective muscular activity. +This postulate applies to all kinds of pain, whatever their cause-- +whether physical injury, pyogenic infection, the obstruction +of hollow viscera, childbirth, etc. + +All forms of pain are associated with muscular action, and as in every +other stimulation of the ceptors, each kind of pain is specific +to the causative stimuli. The child puts his hand in the fire; +physical injury pain results, and the appropriate muscular +response is elicited. If pressure is prolonged on some parts +of the body, anemia of the parts may result, with a corresponding +discomfort or pain, requiring muscular action for relief. +When the rays of the sun strike directly upon the retina, light pain +causes an immediate protective action, so too in the evacuation +of the intestine and the urinary bladder as normal acts, and in +overcoming obstruction of these tracts, discomfort or pain compel +the required muscular actions. This view of pain as a stimulation +to motor action explains why only certain types of infection are +associated with pain; namely, those types in which the infection +may be spread by muscular action or those in which the fixation +of parts by continued muscular rigidity is an advantage. +As a further remarkable proof of the marvelous adaptation +of the body mechanism to meet varying environmental conditions, +we find that just as nociceptors have been implanted in only those +parts of the body which have been subject to nocuous contacts, +so a type of infection which causes muscular action in one part +of the body may cause none when it attacks another. + +This postulate gives us the key to the pain-muscular phenomena +of peritonitis, pleurisy, cystitis, cholecystitis, etc., as well as to +the pain-muscular phenomena in obstructions of the hollow viscera. +If pain is a part of a muscular response and occurs only +as a result of contact ceptor stimulation by physical injury, +infection, anemia, or obstruction, we may well inquire which part +of the nerve mechanism is the site of the phenomenon of pain. +Is it the nerve-ending, the nerve-trunk, or the brain? That is, +is pain associated with the physical contact with the nerve-ending, +or with the physical act of transmission along the nerve-trunk, +or with the change of brain-cell substance by means of which +the motor-producing energy is released? + +We postulate that the pain is associated with the discharge of energy +from the brain-cells. If this be true, then if every nociceptor in +the body were equally stimulated in such a manner that all the stimuli +should reach the brain-cells simultaneously, then the cells would +find themselves in equilibrium and no motor act would be performed. +But if all the pain nerve ceptors but one were equally stimulated, +and this one more strongly stimulated than the rest, then this +one would gain possession of the final common path--would cause +a muscular action and the sensation of pain. + +It is well known that when a greater pain or stimulus is thrown +into competition with a lesser one, the lesser is submerged. +Of this fact the school-boy makes use when he initiates +the novice into the mystery of the painless pulling of hair. +The simultaneous but severe application of the boot to the blindfolded +victim takes complete but exclusive possession of the final common +path and the hair is painlessly plucked as a result of the triumph +of the boot stimulus over the pull on the hair in the struggle +for the final common path. + +Persons who have survived a sudden, complete exposure to superheated steam, +or whose bodies have been enwrapped in flame, testify that they +have felt no pain. As this absence of pain may be due to the fact +that the emotion of fear gained the final common path, to the exclusion +of all other stimuli, we are trying by experimentation to discover +the effects of simultaneous painful stimulation of all parts of the body. +The data already in hand, and the experiments now in progress, +in which anesthetized animals are subjected to powerful stimuli +applied to certain parts of the body only, or simultaneously to +all parts of the body, lead us to believe that in the former case +the brain-cells become stimulated or hyperchromatic, while in the latter +case no brain-cell changes occur. We believe that our experiments +will prove that an equal and simultaneous stimulation of all parts +of the body leaves the brain-cells in a state of equilibrium. +Our theory of pain will then be well sustained, not only by common +observation, but by experimental proof, and so the mechanistic view +will be found in complete harmony with another important reaction. + +We have stated that when a number of contact stimuli act simultaneously, +the strongest stimulus will gain possession of the final common path-- +the path of action. When, however, stimuli of the distance ceptors +compete with stimuli of the contact ceptors, the contact-ceptor +stimuli often secure the common path, not because they are stronger +or more important, but because they are immediate and urgent. +In many instances, however, the distance-ceptor stimuli are strong, +have the advantage of a lowered threshold, and therefore compete +successfully with the immediate and present stimuli of the +contact ceptors. In such cases we have the interesting phenomenon +of physical injury without resultant pain or muscular response. +The distance-ceptor stimuli which may thus triumph over even powerful +contact-ceptor stimuli are those causing strong emotions--as great +anger in fighting; great fear in a battle; intense sexual excitement. +Dr. Livingstone has testified to his complete unconsciousness +to pain during his struggle with a lion; although he was torn +by teeth and claws, his fear overcame all other impressions. +By frequently repeated stimulation the Dervish secures a low +threshold to the emotions caused by the thought of God or the devil, +and his emotional excitement is increased by the presence of others +under the same stimulation; emotion, therefore, secures the final +common path and he is unconscious of pain when he lashes, cuts, +and bruises his body. The phenomena of hysteria may be explained +on this basis, as may the unconsciousness of passing events +in a person in the midst of a great and overwhelming grief. +By constant practice the student may secure the final common path for +such impressions as are derived from the stimuli offered by the subject +of his study, and so he will be oblivious of his surroundings. +Concentration is but another name for a final common path secured +by the repetition and summation of certain stimuli. + +If our premises are sustained, then we can recognize in man no will, +no ego, no possibility for spontaneous action, for every action must +be a response to the stimuli of contact or distance ceptors, or to their +recall through associative memory. Memory is awakened by symbols which +represent any of the objects or forces associated with the act recalled. +Spoken and written words, pictures, sounds, may stimulate the brain +patterns formed by previous stimulation of the distance ceptors; +while touch, pain, temperature, pressure, may recall previous +contact-ceptor stimuli. Memory depends in part upon the adequacy +of the symbol, and in part upon the state of the threshold. +If one has ever been attacked by a snake, the threshold to any +symbol which could recall that attack would be low; the later +recall of anything associated with the bite or its results would +produce in memory a recapitulation of the whole scene, while even +harmless snakes would thereafter be greeted with a shudder. +On the other hand, in a child the threshold is low to the desire +for the possession of any new and strange object; in a child, +therefore, to whom a snake is merely an unusual and fascinating object, +there is aroused only curiosity and the desire for the possession +of a new plaything. + +If we are to attribute to man the possession of a governing +attribute not possessed by other parts of the animal creation, +where are we to draw the boundary line, and say "here the ego-- +the will--the reason--emerges"? What attribute, after all, has man +which in its ultimate analysis is not possessed by the lowest +animals or by the vegetable creation, even? From the ameba, +on through all the stages of animal existence, every action is +but a response to an adequate stimulus; and as a result of adequate +stimuli each step has been taken toward the higher and more +intricate mechanisms which play the higher and more intricate parts +in the great scheme of nature. + +The Venus fly-trap responds to as delicate a stimulus as do +any of the contact ceptors of animals, and the motor activity +resulting from the stimulus is as complex. To an insect-like touch +the plant responds; to a rough contact there is no response; that is, +the motor mechanism of the plant has become attuned to only such +stimuli as simulate the contact of those insects which form its diet. +It catches flies, eats and digests them, and ejects the refuse +(Fig. 47). The ameba does no less. The frog does no more, +excepting that in its place in creation a few more reactions are +required for its sustenance and for the propagation of its species. +Man does no more, excepting that in man's manifold relations +there are innumerable stimuli, for meeting which adequately, +innumerable mechanisms have been evolved. The motor mechanism +of the fly-trap is perfectly adapted to its purpose. +The motor mechanism of man is adapted to its manifold uses, +and as new environmental influences surround him, we must believe +that new adaptations of the mechanism will be evolved to meet +the new conditions. + +Is not this conception of man's activities infinitely more wonderful, +and infinitely more comprehensible than is the conception that his +activities may be accounted for by the existence of an unknown, +unimaginable, and intangible force called "mind" or "soul"? + +We have already shown how the nerve mechanism is so well adapted +to the innumerable stimuli of environment that it can accurately +transmit and distinguish between the infinite variations of speed +in the ether waves producing light, and the air waves producing sound. +Each rate of vibration energizes only the mechanism which has +been attuned to it. With marvelous accuracy the light and sound +waves gain access to the nerve tissue and are finally interpreted +in terms of motor responses, each by the brain pattern attuned +to that particular speed and intensity. So stimuli and resultant +actions multiplied by the total number of the motor patterns +in the brain of man give us the sum total of his life's activities-- +they constitute his life. + +As in evolutionary history the permanence of an adaptation of the body +mechanism depends upon its value in the preservation of the life +of the individual and upon its power to increase the value of +the individual to the race, so the importance and truth of these +postulates and theories may well be judged on the same basis. + +The fundamental instincts of all living matter are self-preservation +and the propagation of the species. The instinct for self-preservation +causes a plant to turn away from cold and damaging winds toward +the life-giving sun; the inert mussel to withdraw within its shell; +the insect to take flight; the animal to fight or to flee; and man +to procure food that he may oppose starvation, to shelter himself +and to provide clothes that he may avoid the dangers of excessive +cold and heat, to combat death from disease by seeking medical aid, +to avoid destruction by man or brute by fight or by flight. +The instinct to propagate the species leads brute man by crude methods, +and cultured man by methods more refined, to put out of his way sex +rivals so that his own life may be continued through offspring. +The life of the species is further assured by the protective +action exercised over the young by the adults of the species. +As soon as the youngest offspring is able successfully to carry on his +own struggle with environment there is no longer need for the parent, +and the parent enters therefore the stage of disintegration. +The average length of life in any species is the sum of the years +of immaturity, plus the years of female fertility, plus the adolescent +years of the offspring. + +The stimuli resulting from these two dominant instincts are now +so overpowering as compared with all other environmental stimuli +that the mere possession of adequate knowledge of the damaging effects +of certain actions as compared with the saving effects of others will +(other things being equal) lead the individual to choose the right,-- +the self- and species-preservative course of action, instead of the wrong,-- +the self- and species-destructive course of action. + +The dissemination of the knowledge of the far-reaching +deleterious effects of protracted emotional strain, of overwork, +and of worry will automatically raise man's threshold to +the damaging activating stimuli causing the strong emotions, +and will cause him to avoid dangerous strains of every kind. +The individual thus protected will therefore rise to a plane +of poise and efficiency far above that of his uncontrolled fellows, +and by so much will his efficiency, health, and happiness be augmented. + +A full acceptance of this theory cannot fail to produce in those +in whose charge rests the welfare of the young, an overwhelming +desire to surround children with those environmental stimuli only +which will tend to their highest ultimate welfare. + +Such is the stimulating force of tradition that many who +have been educated under the tenets of traditional beliefs +will oppose these hypotheses--even violently, it may be. +So they have opposed them; so they opposed Darwin; so they +have opposed all new and apparently revolutionary doctrines. +Yet these persons themselves are by their very actions proving +the efficiency of the vital principles which we have enunciated. +What is the whole social welfare movement but a recognition +on the part of municipalities, educational boards, and religious +organizations of the fact that the future welfare of the race +depends upon the administration to the young of forceful +uplifting environmental stimuli? + +There are now, as there were in Darwin's day, many who feel that man +is degraded from his high estate by the conception that he is not +a reasoning, willing being, the result of a special creation. +But one may wonder indeed what conception of the origin of man can +be more wonderful or more inspiring than the belief that he has +been slowly evolved through the ages, and that all creatures +have had a part in his development; that each form of life has +contributed and is contributing still to his present welfare +and to his future advancement. + + +Recapitulation + +Psychology,--the science of the human soul and its relations,-- +under the mechanistic theory of life, must receive a new definition. +It becomes a science of man's activities as determined by the +environmental stimuli of his phylogeny and of his ontogeny. + +On this basis we postulate that throughout the history of the race nothing +has been lost, but that every experience of the race and of the individual +has been retained for the guidance of the individual and of the race; +that for the accomplishment of this end there has been evolved through +the ages a nerve mechanism of such infinite delicacy and precision +that in some unknown manner it can register permanently within +itself every impression received in the phylogenetic and ontogenetic +experience of the individual; that each of these nerve mechanisms +or brain patterns has its own connection with the external world, +and that each is attuned to receive impressions of but one kind, +as in the apparatus of wireless telegraphy each instrument can +receive and interpret waves of a certain rate of intensity only; +that thought, will, ego, personality, perception, imagination, +reason, emotion, choice, memory, are to be interpreted in terms +of these brain patterns; that these so-called phenomena of human +life depend upon the stimuli which can secure the final common path, +this in turn having been determined by the frequency and the strength +of the environmental stimuli of the past and of the present. + +Finally, as for life's origin and life's ultimate end, +we are content to say that they are unknown, perhaps unknowable. +We know only that living matter, like lifeless matter, has its own +place in the cosmic processes; that the gigantic forces which operated +to produce a world upon which life could exist, as a logical sequence, +when the time was ripe, evolved life; and finally that these cosmic +forces are still active, though none can tell what worlds and what +races may be the result of their coming activities. + + + + +A MECHANISTIC THEORY OF DISEASE[*] + + +[*] Oration in Surgery. Delivered at the 147th Annual Meeting of the +Medical Society of New Jersey, at Spring Lake, N. J., June 11, 1913. + +In this address the paragraphs which were taken from the preceding +paper, "A Mechanistic View of Psychology," have been omitted, +those portions only being republished in which the premises have +been applied in a discussion of certain medical problems rather +than of psychological problems. + + + +The human body is an elaborate mechanism equipped first for such +conflict with environment as will tend to the preservation +of the individual, and second for the propagation of the species, +both of these functions, when most efficiently carried out, +tending to the upbuilding and perfection of the race. +From the date of Harvey's discovery of the circulation of the blood, +to the present day, the human body has been constantly compared +to a machine, but the time for analogy and comparison is past. +I postulate that the body is itself a mechanism responding in every +part to the adequate stimuli given it from without by the environment +of the present and from within by the environment of the past, +the memory of which is stored in the central battery of the mechanism-- +the brain. + * * * * * * * * * * + * * * * * * * * * * + +If the full history of the species and of the individual +could be known in every detail, then every detail of that +individual's conduct in health and disease could be predicted. +Reaction to environment is the basis of conduct, of moral standards, +of manners and conventions, of work and play, of love and hate, +of protection and murder, of governing and being governed, in fact, +of all the reactions between human beings--of the entire web of life. +As Sherrington has stated, "Environment drives the brain, the brain +drives the various organs of the body," and here we believe we find +the key to a mechanistic interpretation of all body processes. + +On this basis we may see that the activities of life depend upon +the ability of the parts of the body mechanism to respond adequately +to adequate stimulation. This postulate applies not only to stimuli +from visible forces, but to those received by the invasion of +the micro-bodies which cause pyogenic or non-pyogenic infections. +In the case of dangerous assaults by visible or invisible enemies, +the brain, through the nerves and all parts of the motor mechanism, +meets the attack by attempts at adaptation. Recovery, invalidism, +and death depend upon the degree of success with which the attacking +or invading enemies are met. Questions regarding disease become, +therefore, questions in adaptation, and it is possible that, +when studied in the light of this conception, the key to many hitherto +unsolved physical problems may be found. + +Perhaps no more convincing proof of our thesis may be secured +than by a study of that ever-present phenomenon--pain. In whatever +part of the body and by whatever apparent cause pain is produced, +we find that it is invariably a stimulation to motor activity-- +whose ultimate object is protection. Thus by the muscular action +resulting from pain we are protected against heat and cold; +against too powerful light; against local anemia caused by prolonged +pressure upon any portion of the body. So, too, pain of greater +or less intensity compels the required emptying of the pregnant +uterus and the evacuation of the intestine and the urinary bladder. + +It should be noted that in every instance the muscular activity +resulting from pain is specific in its type, its distribution, +and its intensity, this specificity being true not only of pain +which is the result of external stimulation, but also of the pain +associated with certain types of infection. + +Pain, however, is not the only symptom of the invasion of +the body by pyogenic or parasitic organisms. Fever, invariably, +and chills, often, accompany the course of the infections. +Can these phenomena also be explained as adaptations of the motor +mechanism for the good of the individual? + +As the phenomena of chills and fever are most strikingly exhibited +in malaria, let us study the course of events in that disease. +It is known that the malarial parasite develops in the red +blood-corpuscles, and that the chills and fever appear when +the cycle of parasitic development is complete and the adults +are ready to escape from the corpuscles of the blood plasma. +Bass, of New Orleans, has proved that the favorable temperature +for the growth of the malarial organism is 98'0, and that at 102'0 +the adult organisms will be killed, though the latter temperature +is not fatal to the spores. The adult life of the malarial +parasite begins after its escape into the blood plasma, and it is +there that the organism is most susceptible to high temperature. +We must infer, therefore, that the fever is an adaptation on the part +of the host for despatching the enemy. + +What, then, may be the protective part played by the chill? +A chill is made up of intermittent contractions of all the external +muscles of the body. This activity results in an increase +of the body heat and in an anemia of the superficial parts +of the body, so that less heat can be lost by radiation. +By this means, therefore, the external portions of the body contribute +measurably to the production of the beneficent and saving fever. + +It must be remembered that this power of adaptation is not peculiar +to man alone, but that it is a quality shared by all living creatures. +While the human body has been adapting itself for self-protection +by producing a febrile reaction whereby to kill the invading organisms, +the invaders on their side have been adapting themselves for a life +struggle within the body of the host. In these mortal conflicts +between invaders and host, therefore, the issue is often in doubt, +and sometimes one and sometimes the other will emerge victorious. + +We must believe that a similar adaptive response exists in all +parasitic infections--the cycles varying according to the stages in +the development of the invaders. If the bacteria develop continuously, +the fever is constant instead of intermittent, since the adequate +stimulus is constantly present. + +Bacteriology has taught us that both heat and cold are fatal +to pathogenic infections; for this reason either of the apparently +contradictory methods of treatment may help, _i. e_., either hot +or cold applications. It should be borne in mind, however, that we have +to deal not only with the adult organisms, but with the spores also. +The application of cold may keep the spores from developing, +while heat may promote their development, and the course of the disease +may vary, therefore, according to our choice of treatment. + +From this viewpoint, we can understand the intermittent temperature +in a patient who is convalescing from an extreme infection, +as peritonitis, pylephlebitis, multiple abscess of the liver, etc. +In these conditions there may occur days of normal temperature, +followed by an abrupt rise which will last for several days-- +this in turn succeeded by another remittance. This cycle may be +repeated several times, and on our hypothesis we may believe it +is caused by the successive development to maturity of spores +of varying ages. + +If these premises are sound, the wisdom of reducing the temperature +in case of infection may well be questioned. + +On this mechanistic basis the emotions also may be explained +as activations of the entire motor mechanism for fighting, +for escaping, for copulating. + * * * * * * * * * * + * * * * * * * * * * + +The emotions, then, are the preparation for phylogenetic activities +(Fig. 48). If the activities were consummated, the fuel--glycogen-- +and the activating secretions from the thyroid, the adrenals, +the hypophysis, would be consumed. In the activation without +action these products must be eliminated as waste products +and so a heavy strain is put upon the organs of elimination. +It is obvious that the body under emotion might be clarified +by active muscular exercise, but the subject of the emotion is so +strongly integrated thereby that it is difficult for him to engage +in diverting, clarifying exertion. + * * * * * * * * * * + * * * * * * * * * * + +So, as we have indicated already, certain deleterious effects are +produced when the body mechanism is activated without resultant action. +For example, the output of adrenalin is increased, and, as a consequence, +arteriosclerosis and cardiovascular disease may occur in persons +who have been subjected to prolonged emotional strain, since it +has been proved that the prolonged administration of adrenalin +will cause these conditions. We have stated that the emotions cause +increased output of glycogen. Glycogen is a step toward diabetes, +and therefore this disease, too, is prone to appear in persons +under emotional strain. It is most common in those races which +are especially emotional in character, so we are not surprised +to find it especially prevalent among Jews. So common is this +particular result of prolonged emotion that some one has said, +"When the stocks go down in New York, diabetes goes up." +Nephritis, also, may result from emotional stress, because of the strain +put upon the kidneys by the unconsumed activating substances. +The increased heart action and the presence of these activating +secretions may cause myocarditis and heart degeneration. +Claudication also may result from the impaired circulation. + +The emotions may cause an inhibition of the digestive secretions +and of intestinal peristalsis. This means that the digestive processes +are arrested, that putrefaction and autointoxication will result, +and that still further strain will thus be put upon the organs +of elimination. Who has not observed in himself and in others when under +the influence of fear, anger, jealousy, or grief that the digestive +processes and general well-being are rapidly and materially altered; +while as tranquillity, peace, and happiness return the physical +state improves accordingly? + +Dentists testify that as a result of continued strong emotion the character +of the saliva changes, pyorrhea develops, and the teeth decay rapidly. +Every one knows that strong emotion may cause the hair to fall +out and to become prematurely gray. + +As to the most important organ of all--the brain--every one is +conscious of its impaired efficiency under emotional strain, +and laboratory researches show that the deficiency is accounted +for by actual cell deterioration; so the individual who day by day +is under heavy emotional strain finds himself losing strength slowly-- +especially do his friends note it. By summation of stimuli +his threshold becomes lowered until stimuli, which under normal +conditions would be of no effect, produce undue responses. +"The grasshopper becomes a burden," and prolonged rest and change +of environmental conditions are necessary for restoration. + +If in a long emotional strain the brain is beaten down; +if the number of "low-efficiency" cells increases, the driving +power of the brain is correspondingly lessened and therefore +the various organs of the body may escape through the very +inefficiency of the brain to produce in them forced activity. +On the other hand, if the brain remains vigorous, the kidneys +may take the strain and break down; if the kidneys do not break, +the blood-vessels may harden; if the blood-vessels are not affected, +the thyroid may become hyperplastic and produce Graves' disease; +if the thyroid escapes, diabetes may develop; while if the iron +constitution of the mechanism can successfully bear the strain +in all its parts, then the individual will break his competitors, +and their mechanisms will suffer in the struggle. + +This whole train of deleterious results of body activation without +action may be best observed and studied in that most emotional +of diseases--exophthalmic goiter. In this disease the constantly +stimulated distance ceptors dispossess the contact ceptors from +the common path, and drive the motor mechanism to its own destruction, +and the patient has the appearance of a person in great terror, +or of a runner approaching the end of a Marathon race (Figs. 16 +and 48 to 54). + +Exophthalmic goiter may result from long emotional or mental stress +in those cases in which the thyroid takes the brunt of the strain upon +the mechanism. As adrenalin increases blood-pressure, so thyroid +secretion increases brain activity, and increased brain activity +in turn causes an increased activation of the motor mechanism +as a whole. + +We know that a deficiency or lack of thyroid secretion will inhibit +sexual emotion and conception, will produce stupidity and inertia; +will diminish vitality. On the other hand, excessive thyroid secretion +drives the entire mechanism at top speed; the emotions are intensified; +the skin becomes soft and moist, the eyes are brilliant and staring; +the limbs tremble; the heart pounds loudly and its pulsations often +are visible; the respiration is rapid; the stimulation of the fear +mechanism causes the eyes to protrude (Fig. 16); the temperature +mounts at every slight provoca-tion and may reach the incredible +height of 110'0 even. In time, the entire organism is destroyed-- +literally consumed--by the concentration of dynamic energy. +It is interesting to note that in these patients emotion gains complete +possession of the final common path; they are wild and delirious-- +but they never have pain. + +All the diseases caused by excessive motor activity may be called +kinetic diseases. Against the conditions in life which produce +them man reacts in various ways. He intro- + + +{illust. caption = FIG. 51.--CROSS-COUNTRY RACE. Winner of six-mile +cross-country race showing typical expression of exhaustion. +(Copyright by Underwood and Underwood, N. Y.) duces restful variety +into his life by hunting and fishing; by playing golf and tennis; +by horseback riding; by cultivating hobbies which effectually. +turn the current of his thoughts{illust. caption = FIG. 52.--{A B +and C} from the consuming stress and strain of his business +or professional life. These diversions are all rational +attempts to relieve tension by self-preservative reactions. +For the same reason man attempts to relieve the strain of +contention with his fellow-man by unions, trusts, corporations. +In spite of all efforts, however, many constitutions are +still broken daily in the fierce conflicts of competition. +We know how often the overdriven individual endeavors to minimize +the activities of his motor mechanism by the use of agents which diminish +brain activity, such as alcohol, tobacco, and various narcotics. +Occasionally also, some person, who can find no respite from his own +relentless energies, seeks relief in oblivion by suicide. + +Most fortunately, two fundamental instincts--self-preservation and +the propagation of the species--act powerfully to prevent +this last fatal result, and instead the harassed individual +seeks from others the aid which is lacking within himself. +He may turn to the priest who seeks and often secures the final +common path for faith in an over-ruling Providence, a faith which in +many incontrovertible instances has proved sufficient in very truth +to move mountains of lesser stimuli; or he turns to a physician, +who too often treats the final outcome of the hyperactivity only. +The physician who accepts the theory of the kinetic diseases, +however, will not only repair as far as he may the lesions caused +by the disordered and forced activities, but will, by compelling and +forceful suggestion, secure the final common path for right conduct, +that is, for a self- and species-preservative course of action +as opposed to wrong conduct-a self- and species-destructive +course of action. + +By forcefully imparting to his patient the knowledge of the far-reaching +effects of protracted emotional strain, of overwork, and of worry, +the physician will automatically raise his threshold to the damaging +activating stimuli which have produced the evil results. +Even though some parts of his organism may have been permanently disabled, +a patient thus protected may yet rise to a plane of poise and +efficiency far above that of his uncontrolled fellows. + +In extreme cases it does not seem unreasonable to believe that the +uncontrolled patient might be rescued by the same principle which has +proved effective in saving patients from the emotional and traumatic strain +of surgical operations--the principle of anoci-association. That is, +by disconnecting one or more of the activating organs from the brain, +the motor mechanism might be saved from its self-destruction. + +Under this hypothesis, that man in disease, as in health, +is the product of his phylogeny as well as of ontogeny, the sphere +of the physician's activities takes on new aspects of far-reaching +and inspiring significance. Prognosis will become definite in proportion +to the physician's knowledge not only of the ontogenetic history of +the individual patient, but also of the phylogenetic history of the race. +As that knowledge increases, as he appreciates more and more keenly +the significance of environment in its effect upon individual development, +in so far will the physician be in a position to contribute mightily +to the welfare of the race. + + + +THE KINETIC SYSTEM[*] + + +[*] Address delivered before the New York State Medical Society, April 28, +1914, to which has been added a further note regarding studies +of hydrogen ion concentration in the blood. + + +In this paper I formulate a theory which I hope will harmonize a large +number of clinical and experimental data, supply an interpretation +of certain diseases, and show by what means many diverse causes +produce the same end effects. + +Even should the theory prove ultimately to be true, it will in the mean +time doubtless be subjected to many alterations. The specialized +laboratory worker will, at first, fail to see the broader clinical view, +and the trained clinician may hesitate to accept the laboratory findings. +Our viewpoint has been gained from a consideration of both lines +of evidence on rather a large scale. + +The responsibility for the kinetic theory is assumed by myself, +while the responsibility for the experimental data is shared fully +by my associates, Dr. J. B. Austin, Dr. F. W. Hitchings, Dr. H. G. Sloan, +and Dr. M. L. Menten.[t] + + +[t] From H. K. Cushing Laboratory of Experimental Medicine, +Western Reserve University, Cleveland. + + +Introduction + +The self-preservation of man and kindred animals is effected +through mechanisms which transform latent energy into kinetic energy +to accomplish adaptive ends. Man appropriates from environment +the energy he requires in the form of crude food which is refined +by the digestive system; oxygen is taken to the blood and carbon +dioxid is taken from the blood by the respiratory system; +to and from the myriads of working cells of the body, food and oxygen +and waste are carried by the circulatory system; the body is cleared +of waste by the urinary system; procreation is accomplished through +the genital system; but none of these systems was evolved primarily +for the purpose of transforming potential energy into kinetic energy +for specific ends. Each system transforms such amounts of potential +into kinetic energy as are required to perform its specific work; +but no one of them transforms latent into kinetic energy for the purposes +of escaping, fighting, pursuing, nor for combating infection. +The stomach, the kidneys, the lungs, the heart strike no physical +blow-their role is to do certain work to the end that the blow may +be struck by another system evolved for that purpose. I propose +to offer evidence that there is in the body a system evolved primarily +for the transformation of latent energy into motion and into heat. +This system I propose to designate "The Kinetic System." + +The kinetic system does not directly circulate the blood, +nor does it exchange oxygen and carbon dioxid; nor does it perform +the functions of digestion, urinary elimination, and procreation; +but though the kinetic system does not directly perform these functions, +it does play indirectly an important role in each, just as the kinetic +system itself is aided indirectly by the other systems. + +The principal organs which comprise the kinetic system are +the brain, the thyroid, the adrenals, the liver, and the muscles. +The brain is the great central battery which drives the body; +the thyroid governs the conditions favoring tissue oxidation; +the adrenals govern immediate oxidation processes; the liver fabricates +and stores glycogen; and the muscles are the great converters +of latent energy into heat and motion. + +Adrenalin alone, thyroid extract alone, brain activity alone, +and muscular activity alone are capable of causing the body temperature +to rise above the normal. The functional activity of no other gland +of the body alone, and the secretion of no other gland alone, can cause +a comparable rise in body temperature--that is, neither increased +functional activity nor any active principle derived from the kidney, +the liver, the stomach, the pancreas, the hypophysis, the parathyroids, +the spleen, the intestines, the thymus, the lymphatic glands, +or the bones can, _per se_, cause a rise in the general body +temperature comparable to the rise that may be caused by the activity +of the brain or the muscles, or by the injection of adrenalin +or thyroid extract. Then, too, when the brain, the thyroid, +the adrenals, the liver, or the muscles are eliminated, the power +of the body to convert latent into kinetic energy is impaired or lost. +I shall offer evidence tending to show that an excess of either +internal or external environmental stimuli may modify one or more +organs of the kinetic system, and that this modification may cause +certain diseases. For example, alterations in the efficiency +of the cerebral link may yield neurasthenia, mania, dementia; +of the thyroid link, Graves' disease, myxedema; of the adrenal link, +Addison's disease, cardiovascular disease. + +This introduction may serve to give the line of our argument. +We shall now consider briefly certain salient facts which relate to +the conversion of latent into kinetic energy as an adaptive reaction. +The experimental data are so many that they will later be published +in a monograph. + +The amount of latent energy which may be converted into kinetic +energy for adaptive ends varies in different species, in individuals +of the same species, in the same individual in different seasons; +in the life cycle of growth, reproduction and decay; +in the waking and sleeping hours; in disease and in activity. +We shall here consider briefly the reasons for some of those variations +and the mechanisms which make them possible. + + +Biologic Consideration of the Adaptive Variation in Amounts +of Energy Stored in Various Animals + +Energy is appropriated from the physical forces of nature +that constitute the environment. This energy is stored in +the body in quantities in excess of the needs of the moment. +In some animals this excess storage is greater than in other animals. +Those animals whose self-preservation is dependent on purely +mechanical or chemical means of defense--such animals as crustaceans, +porcupines, skunks or cobras--have a relatively small amount +of convertible (adaptive) energy stored in their bodies. +On the contrary, the more an animal is dependent on its muscular +activity for self-preservation, the more surplus available +(adaptive) energy there is stored in its body. It may be true that all +animals have approximately an equal amount per kilo of chemical energy-- +but certainly they have not an equal amount stored in a form +which is available for immediate conversion for adaptive ends. +Adaptive Variation in the Rate of Energy Discharge + +What chance for survival would a skunk have without odor; a cobra +without venom; a turtle without carapace; or a porcupine shorn +of its barbs, in an environment of powerful and hostile carnivora? +And yet in such an hostile environment many unprotected animals +survive by their muscular power of flight alone. It is evident that +the provision for the storage of "adaptive" energy is not the only +evolved characteristic which relates to the energy of the body. +The more the self-preservation of the animal depends on motor activity, +the greater is the range of variation in the rate of discharge of energy. +The rate of energy discharge is especially high in animals evolved +along the line of hunter and hunted, such as the carnivora and +the herbivora of the great plains. + + +Influences That Cause Variation in the Rate of Output of Energy +in the Individual + +Not only is there a variation in the rate of output of energy among +various species of animals, but one finds also variations in the rate +of output of energy among individuals of the same species. +If our thesis that men and animals are mechanisms responding to +environmental stimuli be correct, and further, if the speed of energy +output be due to changes in the activating organs as a result of +adaptive stimulation, then we should expect to find physical changes +in the activating glands during the cycles of increased activation. +What are the facts? We know that most animals have breeding +seasons evolved as adaptations to the food supply and weather. +Hence there is in most animals a mating season in advance of +the season of maximum food supply so that the young may appear at +the period when food is most abundant. In the springtime most birds +and mammals mate, and in the springtime at least one of the great +activating glands is enlarged--the thyroid in man and in animals shows +seasonal enlargement. The effect of the increased activity is seen +in the song, the courting, the fighting, in the quickened pulse, +and in a slightly raised temperature. Even more activation +than that connected with the season is seen in the physical state +of mating, when the thyroid is known to enlarge materially, +though this increased activity, as we shall show later, is probably +no greater than the increased activity of other activating glands. +In the mating season the kinetic activity is speeded up; in short, +there exists a state--a fleeting state--of mild Graves' disease. +In the early stages of Graves' disease, before the destructive phenomena +are felt, the kinetic speed is high, and life is on a sensuous edge. +Not only is there a seasonal rhythm to the rate of flow of energy, +but there is a diurnal variation--the ebb is at night, +and the full tide in the daytime. This observation is verified +by the experiments which show that certain organs in the kinetic +chain are histologically exhausted, the depleted cells being +for the most part restored by sleep. + +We have seen that there are variations in speed in different species, +and that in the same species speed varies with the season of the year +and with the time of day. In addition there are variations also in +the rate of discharge of energy in the various cycles of the life +of the individual. The young are evolved at high speed for growth, +so that as soon as possible they may attain to their own power +of self-defense; they must adapt themselves to innumerable bacteria, +to food, and to all the elements in their external environment. +Against their gross enemies the young are measurably protected +by their parents; but the parents--except to a limited extent in +the case of man--are unable to assist in the protection of the young +against infectious disease. + +The cycle of greatest kinetic energy for physiologic ends is the period +of reproduction. In the female especially there is a cycle of increased +activity just prior to her development into the procreative state. +During this time secondary sexual characters are developed-- +the pelvis expands, the ovaries and the uterus grow rapidly, +the mammary glands develop. Again in this period of increasing +speed in the expenditure of energy we find the thyroid, +the adrenals, and the hypophysis also in rapid growth. +Without the normal development of the ovary, the thyroid, +and the hypophysis, neither the male nor the female can develop +the secondary sexual characters, nor do they develop sexual desire +nor show seasonal cycles of activity, nor can they procreate. +The secondary sexual characters--sexual desire, fertility--may be +developed at will, for example, by feeding thyroid products from +alien species to the individual deprived of the thyroid. + +At the close of the child-bearing period there is a permanent +diminution of the speed of energy discharge, for energy is no +longer needed as it was for the self-preservation of the offspring +before adolescence, and for the propagation of the species +during the procreative period. Unless other factors intervene, +this reduction in speed is progressive until senescent death. +The diminished size of the thyroid of the aged bears testimony +to the part the activating organs bear in the general decline. + +We have now referred to variations in the rate of discharge of +energy in different species; in individuals of the same species; +in cycles in the same individual--such as the seasons of food supply, +the periods of wakefulness and of sleep, the procreative period, +and we have spoken of those variations caused artificially +by thyroid feeding, thus far having confined our discussion +to the conversion for adaptive purposes of latent into kinetic +energy in muscular and in procreative action. We shall now consider +the conversion of latent into kinetic energy in the production of +heat,[*] and endeavor to answer the questions which arise at once: +Is there one mechanism for the conversion of latent energy into heat +and another mechanism for its conversion into muscular action? +What is the adaptive advantage of fever in infection? + + +[*] We use the terms "heat" and "muscular action" in the popular sense, +though physicists use them to designate one and the same kind of energy. + +The Purpose and the Mechanism of Heat Production in Infections + +Vaughan has shown that the presence in the body of any alien protein +causes an increased production of heat, and that there is no difference +between the production of fever by foreign proteins and by infections. +Before the day of the hypodermic needle and of experimental medicine, +the foreign proteins found in the body outside the alimentary tract +were brought in by invading microorganisms. Such organisms interfered +with and destroyed the host. The body, therefore, was forced +to evolve a means of protection against these hostile organisms. +The increased metabolism and fever in infection might operate +as a protection in two ways--the increased fever, by interfering +with bacterial growth, and the increased metabolism, by breaking up +the bacteria. Bacteriologists have taught us that bacteria grow best +at the normal temperature of the body, hence fever must interfere +with bacterial growth. With each rise of one degree centigrade +the chemical activity of the body is increased 10 per cent. +In acute infections there is aversion to food and frequently there +is vomiting. In fever, then, we have diminished intake of energy, +but an increased output of energy--hence the available potential +energy in the body is rapidly consumed. This may be an adaptation +for the purpose of breaking up the foreign protein molecules +composing the bacteria. Thus the body may be purified by a chemical +combustion so furious that frequently the host itself is destroyed. +The problems of immunity are not considered here. + +As to the mechanism which produces fever, we postulate that it +is the same mechanism as that which produces muscular activity. +Muscular activity is produced by the conversion of latent energy +into motion, and fever is produced largely in the muscles by +the conversion of latent energy into heat. We should, therefore, +find similar changes in the brain, the adrenals, the thyroid, +and the liver, whatever may be the purpose of the conversion of energy-- +whether for running, for fighting, for the expression of emotion, +or for combating infection. + +We shall first present experimental and clinical evidence which tends +to show what part is played by the brain in the production of both +muscular and febrile action, and later we shall discuss the parts +played by the adrenals, the thyroid, and the liver. Histologic Changes +in the Brain-cells in Relation to the Maintenance of Consciousness +and to the Production of the Emotions, Muscular Activity, and Fever + +We have studied the brain-cells in human cases of fever, +and in animals after prolonged insomnia; after the injection +of the toxins of gonococci, of streptococci, of staphylococci, +and of colon, tetanus, diphtheria, and typhoid bacilli; and after +the injection of foreign proteins, of indol and skatol, of leucin, +and of peptones. We have studied the brains of animals which had been +activated in varying degrees up to the point of complete exhaustion +by running, by fighting, by rage and fear, by physical injury, +and by the injection of strychnin (Figs. 2, 4, 5, and 37). We have +studied the brains of salmon at the mouth of the Columbia River +and at its headwater (Fig. 55); the brains of electric fish, +the storage batteries of which had been partially discharged, +and of those the batteries of which had been completely discharged; +the brains of woodchucks in hibernation and after fighting; +the brains of humans who had died from anemia resulting from hemorrhage, +from acidosis, from eclampsia, from cancer and from other chronic diseases +(Figs. 40 to 43, 56, 74, and 75). We have studied also the brains +of animals after the excision of the adrenals, of the pancreas, +and of the liver (Figs. 57 and 60). + +In every instance the loss of vitality--that is, the loss +of the normal power to convert potential into kinetic energy-- +was accompanied by physical changes in the brain-cells (Figs. 45 +and 46). The converse was also true, that is, the brain-cells +of animals with normal vital power showed no histologic changes. +The changes in the brain-cells were identical whatever the cause. +The crucial question then becomes: Are these constant changes in +the brain-cells the result of work done by the brain-cells in running, +in fighting, in emotion, in fever? In other words, does the brain +perform a definite role in the conversion of latent energy into +fever or into muscular action; or are the brain-cell changes caused +by the chemical products of metabolism? Happily, this crucial +question was definitely answered by the following experiment: +The circulations of two dogs were crossed in such a manner that the +circulation of the head of one dog was anastomosed with the circulation +of the body of another dog, and vice versa. A cord encircled the neck +of each so firmly that the anastomosing circulation was blocked +(Fig. 58). If the brain-cell changes were due to metabolic products, +then when the body of dog "A" was injured, the brain of dog "A" +would be normal and the brain of dog "B" would show changes. +Our experiments showed brain-cell changes in the brain of the dog +injured and no changes in the brain of the uninjured dog. + +The injection of adrenalin causes striking brain-cell changes: +first, a hyperchromatism, then a chromatolysis. Now if adrenalin +caused these changes merely as a metabolic phenomenon and not as a +"work" phenomenon, then the injection of adrenalin into the carotid +artery of a crossed circulation dog would cause no change in its +circulation and its respiration, since the brain thus injected +is in exclusive vascular connection with the body of another dog. +In our experiment the blood-pressures of both dogs were recorded +on a drum when adrenalin was injected into the common carotid. +The adrenalin caused a rise in blood-pressure, an increase +in the force of cardiac contraction, increase in respiration, +and a characteristic adrenalin rise in the blood-pressure of both dogs. +The rise was seen first in the dog whose brain alone received adrenalin +and about a minute later in the dog whose body alone received adrenalin +(Fig. 59). Histologic examinations of the brains of both dogs +showed marked hyperchromatism in the brain receiving adrenalin, +while the brain receiving no adrenalin showed no change. +Here is a clear-cut observation on the action of adrenalin +on the brain, for both the functional and the histologic +tests showed that adrenalin causes increased brain action. +The significance of this affinity of the brain for adrenalin begins +to be seen when I call attention to the following striking facts: + +1. Adrenalin alone causes hyperchromatism followed by chromatolysis, +and in overdosage causes the destruction of some brain-cells. + +2. When both adrenal glands are excised and no other factor +is introduced, the Nissl substance progressively disappears from +the brain-cells until death. This far-reaching point will be taken +up later (Fig. 60). + +Here our purpose is to discuss the cause of the brain-cell changes. +We have seen that in crossed brain and body circulation trauma +causes changes in the cells of the brain which is disconnected +from the traumatized body by its circulation, but which is +connected with the traumatized body by the nervous system. +We have seen that adrenalin causes activation of the body connected +with its brain by the nervous system, and histologic changes in +the brain acted on directly by the adrenalin, but we found no notable +brain-cell changes in the other brain through which the products +of metabolism have circulated. + +In the foregoing we find direct evidence that the products of +metabolism are not the principal cause of the brain-cell changes. +We shall now present evidence to show that for the most part +the brain-cell changes are "work" changes. What work? We postulate +that it is the work by which the energy stored in the brain-cells is +converted into electricity or some other form of transmissible energy +which then activates certain glands and muscles, thus converting latent +energy into beat and motion. It has chanced that certain other studies +have given an analogous and convincing proof of this postulate. +In the electric fish a part of the muscular mechanism is replaced +by a specialized structure for storing and discharging electricity. +We found "work" changes in the brain-cells of electric fish +after all their electricity had been rapidly discharged +(Fig. 61). We found further that electric fish could not discharge +their electricity when under anesthesia, and clinically we +know that under deep morphin narcosis, and under anesthesia, +the production both of heat and of muscular action is hindered. +The action of morphin in lessening fever production is probably +the result of its depressing influence on the brain-cells, because +of which a diminished amount of their potential energy is converted +into electricity and a diminished electric discharge from the brain +to the muscles should diminish heat production proportionally. +We found by experiment that under deep morphinization brain-cell +changes due to toxins could be largely prevented (Fig. 62); +in human patients deep morphinization diminishes the production +of muscular action and of fever and conserves life when it is +threatened by acute infections. The contribution of the brain-cells +to the production of heat is either the result of the direct +conversion of their stored energy into heat, or of the conversion +of their latent energy into electricity or a similar force, +which in turn causes certain glands and muscles to convert latent +energy into heat. + +A further support to the postulate that the brain-cells contribute +to the production of fever by sending impulses to the muscles +is found in the effect of muscular exertion, or of other forms of +motor stimulation, in the presence of a fever-producing infection. +Under such circumstances muscular exertion causes additional fever, +and causes also added but identical changes in the brain-cells. Thyroid +extract and iodin have the same effect as muscular exertion and infection +in the production of fever and the production of brain-cell changes. +All this evidence is a strong argument in favor of the theory that +certain constituents of the brain-cells are consumed in the work +performed by the brain in the production of fever. + +That the stimulation of the brain-cells without gross activity +of the skeletal muscles and without infection can produce heat +is shown as follows: + +(_a_) Fever is produced when animals are subjected to fear without +any consequent exertion of the skeletal muscles. + +(_b_) The temperature of the anxious friends of patients will rise +while they await the outcome of an operation (Fig. 63). + +(_c_) The temperature and pulse of patients will rise as a result +of the mere anticipation of a surgical operation (Fig. 64). + +(_d_) There are innumerable clinical observations as to the effect +of emotional excitation on the temperature of patients. +A rise of a degree or more is a common result of a visit from +a tactless friend. There is a traditional Sunday increase +of temperature in hospital wards. Now the visitor does not bring +and administer more infection to the patient to cause this rise, +and the rise of temperature occurs even if the patient does +not make the least muscular exertion as a result of the visit. +I once observed an average increase of one and one-eighth degrees +of temperature in a ward of fifteen children as a result of a Fourth +of July celebration. + +Is the contribution of the brain to the production of heat due +to the conversion of latent energy directly into heat, or does +the brain produce heat principally by converting its latent energy +into electricity or some similar form of transmissible energy which, +through nerve connections, stimulates other organs and tissues, +which in turn convert their stores of latent energy into heat? + +According to Starling, when the connection between the brain +and the muscles of an animal is severed by curare, by anesthetics, +by the division of the cord and nerves, then the heat-producing power +of the animal so modified is on a level with that of cold-blooded animals. +With cold the temperature falls, with heat it rises. Such an animal +has no more control over the conversion of latent energy into heat +than it has over the conversion of latent energy into motion. + +Electric stimulation done over a period of time causes brain-cell changes, +and electric stimulation of the muscles causes a rise in temperature. + + +Summary of Brain-cell Studies + +In our crossed circulation experiments we found that neither waste +products nor metabolic poisons could be considered the principal +cause of the brain-cell changes. We found that in the production +both of muscular action and of fever there were brain-cell changes +which showed a quantita-tive relation to the temperature changes +or to the muscular work done. We observed that under deep +morphinization the febrile response or the muscular work done was +either diminished or eliminated and that the brain-cell changes were +correspondingly diminished or eliminated. We found also that brain-cell +changes and muscular work followed electric stimulation alone. +I conclude, therefore, that the brain-cell changes are work changes. + +We shall next consider other organs of the kinetic system in their +relation to muscular activity, to emotion, to consciousness, +to sleep, to hibernation, and to heat production. + + +The Adrenals + +In our extensive study of the brain in its relation to the production +of energy and the consequent exhaustion caused by fear and rage; +by the injection of foreign proteins, of bacterial toxins, +and of strychnin; by anaphylaxis; by the injection of thyroid extract, +of adrenalin, and of morphin, we found that, with the exception +of morphin, each of these agents produced identical changes in +the brain-cells. As we believed that the adrenals were intimately +associated with the brain in its activities, we concluded that +the adrenals also must have been affected by each of these agents. +To prove this relation, we administered the above-mentioned +stimuli to animals and studied their effects upon the adrenals +by functional, histologic, and surgical methods, the functional +tests being made by Cannon's method. + +Functional Study of the Adrenals.--Our method of applying +the Cannon test for adrenalin was as follows: (_a_) The blood +of the animals was tested before the application of the stimulus. +If this test was negative, then (_b_) the stimulus was applied +and the blood again tested. If this second test was negative, +a small amount of adrenalin was added. If a positive reaction +was then given, the negative result was accepted as conclusive. +(_c_) If the control test was negative, then the stimulus was given. +If the blood after stimulation gave a positive result for adrenalin, +a second test of the same animal's blood was made twenty-five minutes +or more later. If the second test was negative, then the positive +result of the first test was accepted as conclusive. + +We have recorded 66 clear-cut experiments on dogs, which show that +after fear and rage, after anaphylaxis, after injections of indol +and skatol, of leucin and creatin, of the toxins of diphtheria and +colon bacilli, of streptococci and staphylococci, of foreign proteins, +and of strychnin, the Cannon test for adrenalin was positive. +The test was negative after trauma under anesthesia, and after +intravenous injections of thyroid extract, of thyroglobin, +and of the juices of various organs injected into the same animal from +which the organs were taken. Placental extract gave a positive test. +The test was sometimes positive after electric stimulation +of the splanchnic nerves. On the other hand, if the nerve supply +to the adrenals had been previously divided, or if the adrenals +had been previously excised, then the Cannon test was negative +after the administration of each of the foregoing adequate stimuli. +Blood taken directly from the adrenal vein gave a positive result, +but under deep morphinization the blood from the adrenal vein +was negative, and under deep morphinization the foregoing adequate +stimuli were negative. + +In brief, the agencies that in our brain-cell studies were found to +cause hyperchromatism followed by chromatolysis gave positive results +in the Cannon test for adrenalin (Fig. 62). The one agent which was +found to protect the brain against changes in the Nissl substance-- +morphin--gave a negative result in the Cannon test for adrenalin. +After excision of the adrenals, or after division of their nerve supply, +all Cannon tests for adrenalin were negative. + +Histologic Study of the Adrenals.--Histologic studies of the adrenals +after the application of the adequate stimuli which gave positive +results to the Cannon test for adrenalin are now in progress, +and thus far the histologic studies corroborate the functional tests. + +In hibernating woodchucks, the cells of the adrenal cortex were found +to be vacuolated and shrunken. In one hundred hours of insomnia, +in surgical shock, in strong fear, in exhaustion from fighting, +after peptone injections, in acute infections, the adrenals undergo +histologic changes characteristic of exhaustion (Figs. 66 to 67). + +We have shown that brain and adrenal activity go hand in hand, +that is, that the adrenal secretion activates the brain, and that +the brain activates the adrenals. The fundamental question which now +arises is this: Are the brain and the adrenals interdependent? +A positive answer may be given to this question, for the evidence +of the dependence of the brain upon the adrenals is as clear as is +the evidence of the dependence of the adrenals upon the brain. +(1) After excision of the adrenals, the brain-cells undergo +continuous histologic and functional deterioration until death. +During this time the brain progressively loses its power +to respond to stimuli and there is also a progressive loss +of muscular power and a diminution of body temperature. +(2) {illust. caption = FIG. 66.In our crossed circulation experiments +we found that adrenalin alone could cause increased brain activity, +while histologically we know that adrenalin alone causes an increase +of the Nissl substance. An animal, both of whose adrenals +had been excised, showed no hyperchromatism in the brain-cells +after the injection of strychnin, toxins, foreign proteins, etc. +(3) When the adrenal nerve supply is divided (Cannon-Elliott), then +there is no increased adrenal activity in response to adequate stimuli. + +From these studies we are forced to conclude not only that the brain +and adrenals are interdependent, but that the brain is actually +more dependent upon the adrenals than the adrenals upon the brain, +since the brain deteriorates progressively to death without the adrenals, +while the adrenal whose connection with the brain has been broken +by the division of its nerve supply will still produce sufficient +adrenalin to support life. + +From the strong affinity of the brain-cells for adrenalin which was +manifested in our experiments we may strongly suspect that the Nissl +substance is a volatile, extremely unstable combination of certain +elements of the brain-cells and adrenalin, because the adrenals alone +do not take the Nissl stain and the brain deprived of adrenalin +also does not take Nissl stain. The consumption of the Nissl +substance in the brain-cells is lessened or prevented by morphin, +as is the output of adrenalin; and the consumption of the Nissl +substance is also lessened or prevented by nitrous oxid. +But morphin does not prevent the action of adrenalin injected +into the circulation, hence the control of morphin over energy +expenditure is exerted directly on the brain-cells. Apparently morphin +and nitrous oxid both act through this interference with oxidation +in the brain. We, therefore, conclude that within a certain range +of acidity of the blood adrenalin can unite with the brain-cells +only through the mediation of oxygen, and that the combination +of adrenalin, oxygen, and certain brain-cell constituents +causes the electric discharge that produces heat and motion. +In this interrelation of the brain and the adrenals we have what is, +perhaps, the master key to the automatic action of the body. +Through the special senses environmental stimuli reach the brain +and cause it to liberate energy, which in turn activates certain +other organs and tissues, among which are the adrenals. The increased +output of adrenalin activates the brain to still greater activity, +as a result of which again the entire sympathetic nervous system +is further activated, as is manifested by increased heart action, +more rapid respiration, raised blood-pressure, increased output +of glycogen, increased power of the muscles to metabolize glucose, etc. + +If this conclusion be well founded, we should find corroborative evidence +in histologic changes in that great storehouse of potential energy, +the liver, as a result of the application of each of the adequate +stimuli which produced brain-cell and adrenal changes. + + +The Liver + +Prolonged insomnia, prolonged physical exertion, infections, injections of +toxins and of strychnin, rage and fear, physical injury under anesthesia, +in fact, all the adequate stimuli which affected the brain and +the adrenals, produced constant and identical histologic changes +in the liver--the cells stained poorly, the cytoplasm was vacuolated, +the nuclei were crenated, the cell membranes were irregular, the most +marked changes occurring in the cells of the periphery of the lobules +(Figs. 69 and 70). In prolonged insomnia the striking changes +in the liver were repaired by one seance of sleep. + +Are the histologic changes in the liver cells due to metabolism or toxic +products, or are they "work" changes incident to the conversion of latent +into kinetic energy? Are the brain, adrenals, and liver interdependent? +The following facts establish the answers to these queries: + +(1) The duration of life after excision of the liver is about +the same as after adrenalectomy--approximately eighteen hours. + +(2) The amount of glycogen in the liver was diminished in all the +experiments showing brain-adrenal activity; and when the histologic +changes were repaired, the normal amount of glycogen was again found. + +(3) In crossed circulation experiments changes were found in the liver +of the animal whose brain received the stimulus. + +From these premises we must consider that the brain, the adrenals, +and the liver are mutually dependent on one another for the conversion +of latent into kinetic energy. Each is a vital organ, each equally vital. +It may be said that excision of the brain may apparently cause death +in less time than excision of the liver or adrenals, but this statement +must be modified by our definition of death. If all the brain +of an animal be removed by decapitation, its body may live on for at +least eleven hours if its circulation be maintained by transfusion. +An animal may live for weeks or months after excision of the cerebral +hemispheres and the cerebellum, while an overtransfused animal may +live many hours, days even, after the destruction of the medulla. +It is possible even that the brain actually is a less vital organ +than either the adrenals or the liver. + +In our research to discover whether any other organs should be +included with the brain, the adrenals, and the liver in this mutually +interdependent relation, we hit upon an experiment which throws +light upon this problem. + +Groups of rabbits were gently kept awake for one hundred hours +by relays of students, an experiment which steadily withdrew +energy but caused not the slightest physical or emotional injury +to any of them; no drug, toxin, or other agent was given to them; +they were given sufficient food and drink. In brief, the internal +and external environments of these animals were kept otherwise normal +excepting for the gentle stimuli which insured continued wakefulness. +This protracted insomnia gradually exhausted the animals completely, +some to the point of death even. Some of the survivors were killed +immediately after the expiration of one hundred hours of wakefulness, +others after varying intervals. + +Histologic studies were made of every tissue and organ in the body. +Three organs, the brain, the adrenals, and the liver, and these three only, +showed histologic changes. In these three organs the histologic changes +were marked, and were almost wholly repaired by one seance of sleep. +In each instance these histologic changes were identical with +those seen after physical exertion, emotions, toxins, etc.[*] It +would appear, then, that these three organs take the stress of life-- +the brain is the "battery," the adrenals the "oxydizer," and the liver +the "gasoline tank." This clear-cut insomnia experiment corresponds +precisely with our other brain-adrenal observations. + + +[*] Further studies have given evidence that the elimination of the acids +resulting from energy-transformation as well as the conversion +of energy stored in the kinetic organs causes histologic changes +in the liver, the adrenals, and possibly in the brain. + + +With these three kinetic organs we may surely associate also the +"furnace," the muscles, in which the energy provided by the brain, +adrenals, and liver, plus oxygen, is fabricated into heat and motion. + +Benedict, in his monumental work on metabolism, has demonstrated +that in the normal state, at least, variations in the heart-beat +parallel variations in metabolism. He and others have shown also that +all the energy of the body, whether evidenced by heat or by motion, +is produced in the muscles. In the muscles, then, we find the fourth +vital link in the kinetic chain. The muscles move the body, +circulate the blood, effect respiration, and govern the body temperature. +They are the passive servants of the brain-adrenal-liver syndrome. + +Neither the brain, the adrenals, the liver, nor the muscles, however, +nor all of these together, have the power to change the rate of +the expenditure of energy; to make possible the increased expenditure +in adolescence, in pregnancy, in courting, and mating, in infections. +No one of these organs, nor all of them together, can act as a +pace-maker or sensitizer. The brain acts immediately in response +to the stimuli of the moment; the adrenals respond instantly +to the fickle brain and the effects of their actions are fleeting; +the liver contains fuel only and cannot activate, and the muscles +in turn act as the great furnace in which the final transformation +into available energy is made. The Thyroid + +Another organ--the thyroid--has the special power of governing +the RATE OF DISCHARGE of energy; in other words, the thyroid is the +pace-maker. Unfortunately, the thyroid cannot be studied to advantage +either functionally or histologically, for there is as yet no available +test for thyroid secretion in the blood as there is for adrenalin, +and thyroid activity is not attended by striking histologic changes. +Therefore the only laboratory studies which have been satisfactory +thus far are those by which the iodin content of the thyroid +has been established. Iodin is stored in the colloid lacunae +of the thyroid and, in combination with certain proteins, +is the active agent of the thyroid. + +Beebe has shown that electric stimulation of the nerve supply of +the thyroid diminishes the amount of iodin which it contains, and it +is known that in the hyperactive thyroid in Graves' disease the iodin +content is diminished. The meagerness of laboratory studies, however, +is amply compensated by the observations which the surgeon has been +able to make on a vast scale--observations which are as definite +as are the results of laboratory experiments. + +The brain-cells and the adrenals are securely, concealed from +the eye of the clinician, hence the changes produced in them +by different causes escape his notice, but the thyroid has always +been closely scrutinized by him. The clinician knows that every +one of the above-mentioned causes of increased brain-cell, adrenal, +liver and muscle activity may cause an increase in the activity +of both the normal or the enlarged thyroid; and lie knows only too +well that in a given case of exophthalmic goiter the same stimuli +which excite the brain, the adrenals, the liver, and the muscles +to increased activity will also aggravate this disease. + +The function of the thyroid in the kinetic chain is best evidenced, +however, by its role in the production of fever. Fever results +from the administration of thyroid extract alone in large doses. +In the hyperactivity of the thyroid in exophthalmic goiter one sees +a marked tendency to fever, in severe cases there is daily fever. +In fact, in Graves' disease we find displayed to an extraordinary +degree an exaggeration of the whole action of the kinetic mechanism. + +We have stated that in acute Graves' disease there is a tendency +to the production of spontaneous fever, and that there is a magnified +diurnal variation in temperature which is due to an increased output +of energy in even the normal reaction producing consciousness. In Graves' +disease there is, therefore, a state of intensified consciousness, which is +associated with low brain thresholds to all stimuli--both to stimuli +that cause muscular action and to stimuli that cause fever. The intensity +of the kinetic discharge is seen in the constant fine tremor. +It is evident that the thresholds of the brain have been sensitized. +In this hypersensitization we find the following strong evidence as to +the identity of the various mechanisms for the production of fever. +In the state of superlative sensitization which is seen in Graves' +disease we find that the stimuli that produce muscular movement, +the stimuli that produce emotional phenomena, and the stimuli that +produce fever are as nearly as can be ascertained equally effective. +Clinical evidence regarding this point is abundant, for in +patients with Graves' disease we find that the three types +of conversion of energy resulting from emotional stimulation, +from infection stimulation, and from nociceptor stimulation +(pain), are, as nearly as can be judged, equally exaggerated. +In the acute cases of Graves' disease the explosive conversion +of latent energy into heat and motion is unexcelled by any other +known normal or pathologic phenomenon. Excessive thyroid secretion, +as in thyrotoxicosis from functioning adenomata, and excessive +thyroid feeding, cause all the phenomena of Graves' disease except +the exophthalmos and the emotional facies (Figs. 15 and 23). +The ligation of arteries, the division of its nerve supply, +or the excision of part of the gland, may reverse the foregoing picture +and restore the normal condition. The patient notes the effect +on the second day and often within a week is relatively quiescent. +On the contrary, if there is thyroid deficiency there results +the opposite state, a reptilian sluggishness. + +At will, then, through diminished, normal, or excessive administration +of thyroid secretion, we may produce an adynamic, a normal, +or an excessively dynamic state. By the thyroid influence, +the brain thresholds are lowered and life becomes exquisite; +without its influence the brain becomes a globe of relatively +inert substance. Excessive doses of iodin alone cause +most of the symptoms of Graves' disease. As we have stated, +the active constituent of the thyroid is iodin in a special +protein combination which is stored in the colloidal spaces. +Hence one would not expect to find changes in the cells of the thyroid +gland as a result of increased activity unless it be prolonged. + +We have thus far considered the normal roles played by the brain, +the adrenals the liver, the muscles, and the thyroid in transforming +latent into kinetic energy in the form of heat and motion as an +adaptive response to environmental stimuli. + +The argument may be strengthened, however, by the discussion of +the effect of the impairment of any of these links in the kinetic +chain upon the conversion of latent into kinetic energy. + + +Effect Upon the Output of Energy of Impaired or Lost Function +of Each of the Several Links in the Kinetic Chain + +(1) _The Brain_.--In cerebral softening we may find all the organs +of the body comparatively healthy excepting the brain. +As the brain is physically impaired it cannot normally stimulate +other organs to the conversion of latent energy into heat or +into motion, but, on the contrary, in these cases we find feeble +muscular and intellectual power. I believe also that in patients +with cerebral softening, infections such as pneumonia show a lower +temperature range than in patients whose brains are normal. + +(2) _The Adrenals_.--In such destructive lesions of the adrenals +as Addison's disease one of the cardinal symptoms is a subnormal +temperature and impaired muscular power. Animals upon whom double +adrenalectomy has been performed show a striking fall in temperature, +muscular weakness,--after adrenalectomy the animal may not be able +to stand even,--and progressive chromatolysis. + +(3) _The Liver_.--When the function of the liver is impaired +by tumors, cirrhosis, or degeneration of the liver itself, +then the entire energy of the body is correspondingly diminished. +This diminution of energy is evidenced by muscular and mental weakness, +by diminished response and by gradual loss of efficiency which finally +reaches the state of asthenia. + +(4) _The Muscles_.--It has been observed clinically that if the muscles +are impaired by long disuse, or by a disease such as myasthenia gravis, +then the range of production of both heat and motion is below normal. +This is in agreement with the experimental findings that anesthetics, +curare, or any break in the muscle-brain connection causes diminished +muscular and heat production. + +(5) _The Thyroid_.--In myxedema one of the cardinal symptoms +is a persistently subnormal temperature and, though prone +to infection, subjects of myxedema show but feeble febrile response +and readily succumb. This clinical observation is strikingly +confirmed by laboratory observations; normal rabbits subjected +to fear showed a rise in temperature of from one to three degrees, +while two rabbits whose thyroids had been previously removed and who +had then been subjected to fright showed much less febrile response. +Myxedema subjects show a loss of physical and mental energy +which is proportional to the lack of thyroid. Deficiency in any +of the organs of the kinetic chain causes alike loss of heat, +loss of muscular and emotional action, of mental power, and of the power +of combating infections--the negative evidence thus strongly supports +the positive. By accumulating all the evidence we believe we +are justified in associating the brain, the adrenals, the thyroid, +the muscles, and the liver as vital links in the kinetic chain. +Other organs play a role undoubtedly, though a minor one. + + +Studies in Hydrogen Ion Concentration in Activation of the Kinetic System + +Having established the identity of some, at least, of the organs +which constitute the kinetic chain, we endeavored to secure still +further evidence regarding the energy-transforming function of these +organs by making studies of the H-ion concentration of the blood, +as one would expect, _prima facie_, that the normal reaction would +be altered by kinetic activation.[*] + + +[*] The H-ion observations were made in my laboratory by Dr. M. L. Menten. + + +H-ion concentration tests were made after the application +of the adequate stimuli by which the function of the kinetic +organs had been determined, and we studied also the effect upon +the acidity of the blood of strychnin convulsions after destruction +of the medulla; of deep narcotization with morphin before anesthesia; +of deep narcotization with morphin after the H-ion concentration +had already been increased by fear, by anger, by exertion, +by injury under anesthesia, or by anesthesia alone. + +The complete data of these experiments will be later reported in +a monograph; here it is sufficient to state that anger, fear, injury, +muscular exertion, inhalation anesthesia, strychnin, alcohol, in fact, +all the stimuli which we had already found to produce histologic +changes in the brain, the adrenals, and the liver-excepting +bacterial toxins--caused increased H-ion concentration. +Of striking significance is the fact that morphin alone caused +no change in the H-ion concentration, while if administered before +the application of a stimulus which by itself produced increased +H-ion concentration, the action of that stimulus was neutralized +or postponed. If, however, morphin was administered after increased +acidity had been produced by any stimulus, or by inhalation anesthesia, +then the time required for the restoration of the normal alkalinity +was much prolonged, and in some instances the power of acid +neutralization was permanently lost. + +After excision of the liver, the normal H-ion concentration +was maintained for periods varying from one to several hours, +after which the concentration (acidity) began to increase as +the vitality of the animal began to decline, the concentration +(acidity) increasing rapidly until death. After excision of +the adrenals the blood remained normal for from four to six hours, +when the H-ion concentration increased rather suddenly, +the increase being synchronous with the incidence of the phenomena +which immediately preceded death. + +In none of these cases was it determined whether the increased +H-ion concentration was due to other causes of death or whether +death was due to the increased acidity. + +It is also significant that after the application of each of +the adequate stimuli which increased the H-ion concentration +of the blood in other parts of the body the blood from the adrenal +vein showed a slight diminution in acidity, as, in most instances, +did the blood from the hepatic vein also. + +In fact, the H-ion concentration of the blood in the adrenal vein +was less than in the blood of any other part of the circulation. + + +Kinetic Diseases + +If our conclusions are sound, then in the kinetic system we find +an explanation of many diseases, and having found the explanation, +we may find new methods of combating them. + +When the kinetic system is driven at an overwhelming rate of speed,-- +as by severe physical injury, by intense emotional excitation, +by perforation of the intestines, by the pointing of an abscess +into new territory, by the sudden onset of an infectious disease, +by an overdose of strychnin, by a Marathon race, by a grilling fight, +by foreign proteins, by anaphylaxis,--the result of these acute +overwhelming activations of the kinetic system is clinically +designated shock, and according to the cause is called traumatic shock, +toxic shock, anaphylactic shock, drug shock, etc. + +The essential pathology of shock is identical whatever the cause. +If, however, instead of an intense overwhelming activation, +the kinetic system is continuously or intermittently overstimulated +through a considerable period of time, as long as each of the links +in the kinetic chain takes the strain equally the result will be +excessive energy conversion, excessive work done; but usually, +under stress, some one link in the chain is unable to take the strain +and then the evenly balanced work of the several organs of the kinetic +system is disturbed. If the brain cannot endure the strain, +then neurasthenia, nerve exhaustion, or even insanity follows. +If the thyroid cannot endure the strain, it undergoes hyperplasia, +which in turn may result in a colloid goiter or in exophthalmic goiter. +If the adrenals cannot endure the strain, cardiovascular disease +may develop. If the liver cannot take the strain, then death from +acute acidosis may follow, or if the neutralizing effect of the liver +is only partially lost, then the acidity may cause Bright's disease. +Overactivation of the kinetic system may cause glycosuria and diabetes. + +Identical physical and functional changes in the organs of +the kinetic system may result from intense continued stimulation +from any of the following causes: Excessive physical labor, +athletic exercise, worry or anxiety, intestinal autointoxication, +chronic infections, such as oral sepsis, tonsillitis, and adenoids; +chronic appendicitis, chronic cholecystitis, colitis, and skin infections; +the excessive intake of protein food (foreign protein reaction); +emotional strain, pregnancy, stress of business or professional life-- +all of which are known to be activators of the kinetic system. + +From the foregoing statements we are able to understand +the muscular weakness following fever; we can understand why +the senile have neither muscular power nor strong febrile reaction; +why long-continued infections produce pathologic changes in the organs +constituting the kinetic chain; why the same pathologic changes +result from various forms of activation of the kinetic system. +In this hypothesis we find a reason why cardiovascular disease may +be caused by chronic infection, by auto-intoxication, by overwork, +or by emotional excitation. We now see that the reason why we find +so much difficulty in differentiating the numerous acute infections +from each other is because they play upon the same kinetic chain. +Our postulate harmonizes the pathologic democracy of the kinetic organs, +for it explains not only why, in many diseases, the pathologic +changes in these organs are identical, but why the same changes +are seen as the result of emotional strain and overwork. +We can thus understand how either emotional strain or acute or chronic +infection may cause either exophthalmic goiter or cardiovascular disease; +how chronic intestinal stasis with the resultant absorption of +toxins may cause cardiovascular disease, neurasthenia, or goiter. +Here is found an explanation of the phenomena of shock, whether the +shock be the result of toxins, of infection, of foreign proteins, +of anaphylaxis, of psychic stimuli, or of a surgical operation +with its combination of both psychic and traumatic elements. + +This conception of the kinetic system has stood a crucial test by making +possible the shockless operation. It has offered a plausible explanation +of the cause and the treatment of Graves' disease. Will the kinetic +theory stand also the clinical test of controlling that protean +disease bred in the midst of the stress of our present-day life? +Present-day life, in which one must ever have one hand on the sword and +the other on the throttle, is a constant stimulus of the kinetic system. +The force of these kinetic stimuli may be lessened at the cerebral +link by intelligent control--a protective control is empirically +attained by many of the most successful men. The force of the kinetic +stimuli may be broken at the thyroid link by dividing the nerve supply, +reducing the blood supply, or by partial excision; or if the adrenals +feel the strain, the stimulating force may be broken by dividing +their nerve supply, reducing the blood supply, or by partial excision. +No theory is worth more than its yield in practice, but already we +have the shockless operation, the surgical treatment of Graves' +disease, and the control of shock and of the acute infections +by overwhelming morphinization (Figs. 62, 72, and 73). + + +Conclusions + +To become adapted to their environment animals are transformers of energy. +This adaptation to environment is made by means of a system of organs +evolved for the purpose of converting potential energy into heat +and motion. The principal organs and tissues of this system are +the brain, the adrenals, the thyroid, the muscles, and the liver. +Each is a vital link, each plays its particular role, and one cannot +compensate for the other. A change in any link of the kinetic +chain modifies proportionately the entire kinetic system which is +no stronger than its weakest link. + +In this conception we find a possible explanation of many diseases +one which may point the way to new and more effective therapeutic +measures than those now at our command. + + + +ALKALESCENCE, ACIDITY, ANESTHESIA--A THEORY OF ANESTHESIA[*] + + +[*] Paper delivered before the Virginia Medical Association, +Washington, D. C., October 29, 1914. + + +Alkalis and bases compose the greater part of the food of man +and animals, the blood in both man and animals under normal conditions +being slightly alkaline or rather potentially alkaline; that is, +although in circulating blood the concentration of the OH-ions-- +upon which the degree of alkalinity depends--is but little more +than in distilled water, yet blood has the power of neutralizing +a considerable amount of acid (Starling, Wells). At the time of death, +whatever its cause, the concentration of H-ions in the blood increases,-- +the concentration of H-ions being a measure of acidity,--that is, +the potential or actual alkalinity decreases and the blood becomes +actually neutral or acid. + +To determine what conditions tend to diminish the normal alkalinity +of the blood, many observations were made for me in my laboratory +by Dr. M. L. Menten to determine by electric measurements +the H-ion concentration of the blood under certain pathologic +and physiologic conditions. + +As a result of these researches we are able to state that the H-ion +concentration of the blood--its acidity--is increased by excessive +muscular activity; excessive emotional excitation; surgical shock; +in the late stages of infection; by asphyxia; by strychnin convulsions; +by inhalation anesthetics; after excision of the pancreas, and in the late +stages of life after excision of the liver and excision of the adrenals. +Morphin and decapitation cause no change in the H-ion concentration. +Ether, nitrous oxid, and alcohol produce an increased acidity +of the blood which is proportional to the depth of anesthesia. + +Many of the cases studied were near death, as would be expected, +since it is well known that a certain degree of acidity is +incompatible with life. + +Since alkalis and bases preponderate in ingested food; +since alkalinity of the blood is diminished by bodily activity; +and since at the point of death the blood is always acid, we may +infer that some mechanism or mechanisms of the body were evolved +for the purpose of changing bases into acids that thus energy +might be liberated. + +These observations lead naturally to the question, May not +acidity of itself be the actual final cause of death? +We believe that it may be so from the facts that--(1) +The intravenous injection of certain acids causes death quickly, +but that convulsions do not occur, since the voluntary muscles +lose their power of contraction; and (2) the intravenous injection +of acids causes extensive histologic changes in the brain, +the adrenals, and the liver which resemble the changes invariably +caused by activation of the kinetic system (Figs. 74 and 75). In view +of these facts may we not find that anesthesia and many instances +of unconsciousness are merely phenomena of acidity? + +As has been stated already, we have found that the H-ion concentration +of the blood--its acidity--is increased by alcohol, by ether, +and by nitrous oxid. In addition our tests have shown that under +ether the increase of the H-ion concentration--acidity--is more +gradual than under nitrous oxid, an observation which accords well +with the fact that nitrous oxid more quickly induces anesthesia +than does ether. + +Further striking testimony in favor of the hypothesis that +the production of acidity by inhalation anesthetics is the method +by which anesthesia itself is produced is found in the fact +that although lethal doses of acid cause muscular paralysis, +yet this paralysis may be mitigated by adrenalin--which is alkaline. +This observation may explain in part the remarkable success of +the method of resuscitation devised by me, in which animals "killed" +by anesthetics and asphyxia are revived by the use of adrenalin. + +In animals under inhalation anesthesia Williams found that no +nerve-current could be detected by the Einthoven string galvanometer, +a fact which might be explained by postulating that nerve-currents +can flow from the brain to the muscles and glands only when there +is a difference of potential. Any variation from the normal +alkalinity of the body must change the difference in potential. +Since the nerve-currents in animals under anesthesia are not demonstrable +by any apparatus at our command, and since anesthesia produces acidity, +then we may infer that acidity reduces the difference in potential. +As long as there is life, a galvanometer of sufficient delicacy +would perforce detect, a nerve-current until the acidity increased +to such a point as to reduce the difference in potential to zero-- +the point of death. If at this point a suitable alkali-- +adrenalin solution--can be introduced quickly enough, the vital difference +in potential may be restored and the life processes will be renewed. +Bearing especially on this point is the fact that if adrenalin +in sufficient quantities be administered simultaneously with an acid, +it will not only prevent the fall in blood-pressure usually +caused by the acid, but will also prevent the histologic changes +in the brain, adrenals, and liver which are usually caused by +the intravenous injection of acids. + +This hypothesis regarding the cause of anesthesia and unconsciousness +explains and harmonizes many facts. It explains how asphyxia, +overwhelming emotion, and excessive muscular exertion, by causing acidity, +may produce unconsciousness. It explains the acidosis which results +from starvation, from uremia, from diabetes, from Bright's disease, +and supplies a reason for the use of intravenous infusions of sodium +bicarbonate to overcome the coma of diabetes and uremia (Fig. 76). +It may explain the quick death from chloroform and nitrous oxid; +and may perhaps show why unconsciousness is so commonly the immediate +precursor of death. + +One of the most noticeable immediate effects of the administration +of an inhalation anesthetic is a marked increase in the rapidity +and force of the respiration. The respiratory center has evidently +been evolved to act with an increase of vigor which is proportional-- +within certain limits--to the increase in the H-ion concentration, +whereas the centers governing the voluntary muscles are inhibited. +In this antithetic reaction of the higher cortical centers and the lower +centers in the medulla to acidity we find a remarkable adaptation +which prevents the animal from killing itself by the further increase +in acidity which would be produced by muscular activity. That is, +as the acidity produced by muscular action increases and threatens life, +the respiratory action, by which carbon dioxid is eliminated and +oxygen supplied, is increased, while the driving power of the brain, +which produces acidity, is diminished or even inhibited entirely; +that is, the state of unconsciousness or anesthesia is reached. +We conclude first that, without this life-saving regulation, +animals under stress would inevitably commit suicide; and, second, +that it is probable that the remarkable phenomenon of anesthesia-- +the coincident existence of unconsciousness and life--is due to this +antithetic action of the cortex and the medulla. + +In the human, as in the animal, the degree of acidity parallels +the depth of inhalation anesthesia. + +Within a few seconds after beginning nitrous oxid anesthesia the acidity +of the blood is increased. This rapid acidulation is synchronous +with almost instantaneous unconsciousness and increased respiration. +If the oxygen in the inhaled mixture be increased, a decrease in +acidity is again synchronous with lighter anesthesia and a decrease +in the respiratory rate. + +If these premises be sound, we are justified in asserting that the state +of anesthesia is due to an induced acidity of the blood. If the acidity +is slight, then the anesthesia is slight and the force of the nerve +impulses is lessened, but the patient is still conscious of them. +As the acidity increases associative memory is lost, and the patient +is said to be unconscious: the centers governing the voluntary muscles +are not inhibited, however, and cutting the skin causes movements. +If the acidity is further increased, there is loss of muscular tone +and even the strong contact ceptor stimuli of a surgical operation +do not cause any muscular response, and, finally, the acidity may be +increased to the point at which the respiratory and circulatory centers +can no longer respond by increased effort, and anesthetic death-- +that is, ACID death--follows. + +Certain clinical phenomena are clarified by this theory and serve +to substantiate it. For example, it is well known that inhalation +anesthesia precipitates the impending acidosis which results +from starvation, from extreme Graves' disease, from great exhaustion, +from surgical shock, and from hemorrhage, and which is present +when death from any cause is imminent. + +We see, therefore, that anesthesia is made possible, first, by the fact +that inhalation anesthetics cause acidity, and, second, by the antithetic +adaptation of the higher centers in the brain and of the centers +governing respiration and circulation. + +In deep contrast to the action of inhalation anesthetics is that +of narcotics. Deep narcotization with morphin and scopolamin is +induced slowly; the respiratory and pulse-rate are progressively lessened-- +and there is no acidity. + +By our researches we have established in what consists the generic +difference between inhalation anesthetics and narcotics. +In our experiments no increase in the H-ion concentration was produced +by morphin or by scopolamin, no matter how deep the narcotization. +In animals already narcotized by morphin the production of acid by any +of the acid-producing stimuli was delayed or prevented. On the other hand, +in animals in which an acidity had already been produced by ether, +by shock, by anger, or by fear, the later administration of morphin +delayed or inhibited entirely the neutralization of the acidity. +In other words, morphin interferes with the normal mechanism by +which acidity is neutralized possibly because its inhibiting action +on the respiratory center is sufficient to overcome the stimulating +action of acidity on that center, for, as we have stated, +the neutralization of acidity is in large measure accomplished +by the increased respiration induced by the acidity itself. + + +SUMMARY + +Acidity inhibits the functions of the cerebral cortex, +but stimulates those of the medulla. This antithetic reaction +to the stimulus of increased H-ion concentration is an adaptation +to prevent animals from committing suicide by over-activity, +for the mechanism for the initiation and control of the +transformation of energy is in the higher centers of the brain, +while an essential part of the mechanism for the neutralization +of acidity--the centers governing circulation and respiration-- +is in the medulla. This explains many clinical phenomena-- +why excessive acidity causes paralysis, why there is great thirst +after inhalation anesthesia, after excessive muscular activity, +excessive emotion--after all those activities which we have found +to be acid-producing, for water, like air, neutralizes acids. +The excessive use of alcohol, anesthetics, excessive work, +intense emotion, all produce lesions of the kidney and of the liver. +The explanation is found in the fact that all these stimuli +increase the acidity of the blood. and that, if long continued, +the neutralizing mechanism must be broken down and so the end-products +of metabolism are insufficiently prepared for elimination. + +In view of these considerations we may well conclude that the maintenance +of the normal potential alkalinity of the blood is to be estimated +as the keystone of the foundation of life itself. + + + +INDEX + +ABDOMEN, diseases of, phylogenetic association and, 44 Acidity, +227 Adaptive energy, 176 variation in rate of energy discharge, +177 Adrenalin, Cannon's test for, 134, 196 injection of, +changes in brain-cells from, 186 Adrenals, 196 brain and, +relation of, 1.98 diseases of, effect of, on output of energy, +216 functional study of, 196 histologic study of, 198 Alcohol, +changes in brain-cells from, 116 Alkalescence, 227 Anemia, pain of, +77 Anesthesia, 2, 227 anoci-association and, differentiation, 34 effect +of trauma under, upon brain that remains awake, 3 inhalation, +cause of exhaustion of brain-cells as result of trauma under, +8 theory of, 227 Anger, 63, 70 Anoci-association, 34 anesthesia +and, differentiation, 34 Graves' disease and, 36 prevention +of shock by application of principle of, 36 Aristotle, 127 Asher, +:37 Associational centers, dulled, 47 Austin, 2, 55, 173 + +BASS, 159 Beebe, 213 Benedict, 212 Biologic consideration of +adaptive variation in amounts of energy stored in various animals, +176 Brain, adrenals and, relation of, 198 diseases of, effect of, +on output of energy, 216 effect of trauma under anesthesia oil, +3 functions, physical state of brain-cells and, relation between, +111 influence of fear on, 64 Brain-cells, cause of exhaustion +of as result of trauma under inhalation anesthesia, 8 changes in, +from alcohol, 116 from drugs, 113 from fatigue, 112 from fear, +112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform, +116 from strychnin, 113 in Graves' disease, 116 in infections, +116 in insanity, 120 in insomnia, 119 histologic changes in, +in relation to maintenance of consciousness and to production +of emotions, muscular activity, and fever, 182 physical state, +brain functions and, relation between, 111 + +CANNON, 57, 64, 68, 73, 133, 138, 196, 202 Cannon's test +for adrenalin, 134, 196 Cells, brain-, cause of exhaustion of, +as result of trauma under inhalation anesthesia, 8 changes in, +from alcohol, 116 from drugs, 113 from fatigue, 112 from fear, +112 from hemorrhage, 113 from injection of adrenalin, 186 from iodoform, +116 from strychnin, 113 in Graves' disease, 116 in infections, +116 in insanity, 120 in insomnia, 119 histologic changes in, in relation +to maintenance of consciousness and to production of emotions, +muscular activity, and fever, 182 physical state, brain functions and, +relation between, Ill Chemical noci-association in infections, +48 Cold pain, 83 sweat, 27 Contact pain, special, 78 Crying, +90 in exophthalmic goiter, 106 + +DARWIN, 12, 26, 30, 91, 127, 153 on phenomena of fear, 26 Disease, +mechanistic theory of, 157 Distance receptors, discharge of energy +through stimulation of, 25 Dog, spinal, 4 Dolley, 2, 10 Drugs, +changes in brain-cells from, 113 + +ELIOT, 1 Elliott, 202 Energy, adaptive, 176 Energy, discharge, rate of, +adaptive variation in, 177 nervous, cause of discharge of, +12 as result of trauma under inhalation anesthesia, 12 discharge of, +role of summation in, 30 through representation of injury, +25 through stimulation of distance receptors, 25 psychic discharge, +25 output of, effect of diseases of adrenals on, 216 of brain on, +216 of liver on, 216 of muscles on, 216 of thyroid on, 217 rate +of out put, influences that cause variation in, 177 Environment, +128, 130 Evacuation pain, 77 Exophthalmic goiter, 66 crying in, +106 fear and, resemblance between, 68 laughing in, 106 + +FATIGUE, changes in brain-cells from, 112 Fear, 26, 52, 55 changes +in brain-cells from, 112 Darwin on phenomena of, 26 Graves' +disease and, resemblance between, 68 influence of, on brain, +61 phenomena of, 56 Fly-trap, Venus', 151 Frankel, 68 Frazier, +82 Functional study of adrenals, 196 + +GOITER, exophthalmic, 66 crying in, 106 Goiter, exophthalmic, fear and, +resemblance between, 68 laughter in, 106 Graves' disease, 66 +anoci-association and, 36 changes in brain-cells in, 116 crying in, +106 fear and, resemblance between, 68 laughter in, 106 + +HARVEY, 1,57 Headache, 80 Heat pain, 77 production in infections, +purpose and mechanism, 180 Hemorrhage, changes in brain-cells from, +113 Hippocrates, 127 Histologic changes in liver, 205 study of adrenals, +198 Hitchings, 173 Hodge, 10 Hornaday, 26 Hydrogen ion concentration +in activation of kinetic system, 217 Hyperthyroidism, 42 + +INFECTIONS, changes in brain-Cells in, 116 chemical noci-association in, +48 heat production in, purpose and mechanism, 180 pain of, +79 Inhalation anesthesia, cause of exhaustion of brain-cells as result +of trauma under, 8 trauma under, cause of discharge of nervous energy +as result of, 12 Insanity, changes in brain-cells in, 120 Insomnia, +changes in brain-cells in, 119 effect of, 205 + +Iodoform, changes in brain-cells from, 116 + +KINETIC diseases, 219 reaction, 93 system, 173 + +LABOR pains, 79 Laughter, 90 causes of, 91 in exophthalmic goiter, +106 Law, Sherrington's, 24 Light pain, 77 Liver, diseases of, effect of, +on output of energy, 216 histologic changes in, 205 Livingstone, +148 Lower, 42 + +MALARIA, 159 McKenzie, 162 Mechanistic theory of disease, 157 view +of psychology, 127 Medical problems, phylogenetic association +in relation to, 1 Menten, 2, 55, 173, 218, 227 Muscles, diseases of, +effect of, on output of energy, 216 + +NAGGING, 46 Nausea pains, 78 Nervous energy, cause of discharge of, +12 as result of trauma under inhalation anesthesia, 12 discharge of, +role of summation in, 30 through representation of injury, +25 through stimulation of distance receptors, 25 psychic discharge, +25 Neurasthenia, sexual, 43 Neuroses, postoperative, 46 traumatic, +46 Noci-association, chemical, in infections, 48 Nociceptors, +14 diseases and injuries of regions not endowed with, 47 + +PAIN, 77, 107, 144, 158 cold, 83 contact, special, 78 evacuation, +77 heat, 77 labor, 78 light, 77 nausea, 78 of anemia, 77 of infection, +79 pleasure, 78 post-operative, 89 site of, 83 traumatic, 89 Personality, +47 Phylogenetic association, diseases of abdomen and, 44 in relation +to certain medical problems, 1 to emotions, 55 Pleasure pains, +78 Postoperative neuroses, 46 pain, 89 Propagation of species, +152 Psychic discharge of energy, 25 Psychology, mechanistic view, 127 + +REACTION, kinetic, 93 Receptors, distance, discharge of energy +through stimulation of, 25 sexual, 53 ticklish, 19 + +SELF-PRESERVATION, 152 Sexual neurasthenia, 43 Sexual receptors, +53 Sherrington, 12, 13, 14, 24, 25, 48, 52, 132, 136, 158 Sherrington's +law, 24 Shock, prevention of, by application of principle of +anoci-association, 36 Sloan, 2, 14, .55, 173 Spinal dog, 4 Starling, +195, 227 Strychnin, changes in brain-cells from, 113 Summation, +role of, in discharge of nervous energy, 30 Sweat, cold, 27 + +TEST, Cannon's, for adrenalin, 134, 196 Thyroid gland, 213 diseases of, +effect of, on output of energy, 217 Ticklish receptors, +19 Trauma, cause of exhaustion of brain-cells as result of, +under inhalation anesthesia, 8 effect of, under anesthesia, +upon brain that remains awake, 3 under inhalation anesthesia, +cause of discharge of nervous energy as result of, 12 Traumatic neuroses, +46 pain, 89 + +VAUGHAN, 180 Venus' fly-trap, 149, 151 + +WEEPING, 90 Welch, 1 Wells, 227 Williams, 231 Worry, 74 + + + + + +End of The Project Gutenberg Etext of Origin and Nature of Emotions** + |